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Sample records for ischemic canine myocardium

  1. Small vessel hematocrit in ischemic myocardium

    SciTech Connect

    Gumm, D.C.; Cooper, S.M.; Marcus, M.L.; Chilian, W.M.; Harrison, D.G.

    1986-03-01

    As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement of retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.

  2. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing. PMID:25102201

  3. Heat shock proteins, end effectors of myocardium ischemic preconditioning?

    PubMed Central

    Guisasola, María Concepcion; Desco, Maria del Mar; Gonzalez, Fernanda Silvana; Asensio, Fernando; Dulin, Elena; Suarez, Antonio; Garcia Barreno, Pedro

    2006-01-01

    The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our “classic” preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called “second protection window.” PMID:17009598

  4. Failure of interventions to maintain mitochondrial function in ischemic myocardium.

    PubMed

    Clements, I P; Dewey, J D; Harrison, C E

    1980-10-01

    The purpose of this study was to investigate whether pyruvate (2.5 mmol/kg), the combination of glucose (3.9 mmol/kg) and insulin (0.13 unit/kg) with potassium (9.27 meq/kg), or sodium dichloroacetate (120 mg/kg) infused for 15 minutes before and 20 minutes after ligation of the left anterior descending coronary arterv in anesthetized dogs restricted the depression in mitochondrial respiratory function induced by ischemia. Myocardial blood flow after ligation in the three groups was o.2 ml/min per gram or less in ischemic subendocardium and was similar to that in saline-infused controls that had also undergone coronary artery ligation. The depressions induced in mitochondrial respiratory control index and state 3 respiration by ischemia in the subendocardium and subepicardium of the three treatment groups, when compared with corresponding nonischemic tissue, were not significantly improved from the control values. It was concluded that these three interventions fail to preserve mitochondrial respiration in ischemic myocardium. PMID:6997645

  5. Colored microspheres reveal interarterial microvascular anastomoses in canine myocardium.

    PubMed

    Cicutti, N; Rakusan, K; Downey, H F

    1992-01-01

    While the presence of microvascular intercommunication within an individual myocardial arterial bed is well documented, there is a paucity of data to support the existence of anastomoses emanating from independent arterial beds. Simultaneous in-vivo infusion of two different colored microsphere suspensions into the left anterior descending (LAD) and left circumflex (LCx) coronary arteries identified a specific interface region of canine myocardium that was perfused by both arterial branches. Subsequent microscopic/morphometric analysis of 40 microns serial sections in eight hearts revealed clustering of microspheres in their respective perfusion territories (red microspheres in the LAD region away from the interface, blue microspheres in the LCx field away from the interface), along with a mutually perfused borderzone. In each tissue section, two regions within this zone were identified and their maximum widths measured. One region was defined as the Interface Transition Zone (ITZ) (mean width = 5251 +/- 770 microns; mean +/- SD). This region was formed by an intermingling of microvessels supplied by the parent arteries of the adjacent perfusion territories; it separated tissue containing only one or the other colored microspheres. The second region was defined as the Boundary Watershed Zone (BWZ) (mean zone width = 3151 +/- 611 microns; mean +/- SD). This region was formed by capillaries containing sphere aggregates of both colors; it was located exclusively within the ITZ. In addition, the ITZ and BWZ were significantly wider in subepicardial than in subendocardial regions (p less than 0.001). PMID:1417709

  6. Detection of ischemic myocardium with a new hypoxic tissue targeting tracer 99Tc(m)-HL91.

    PubMed

    Lü, Jiagao; Liu, Gang; Fang, Ya; Wu, Hua

    2006-01-01

    The imaging appearances of 99Tc(m)-HL91, a new hypoxic imaging agent, in ischemic myocardium were studied and the value of 99Tc(m)-HL91 in the evaluation of regional ischemic viable myocardium was explored. Acute myocardial ischemia models were made by coronary artery legations in 18 rats and randomly divided into 2 groups: 99Tc(m)-HL91 group and 99Tc(m)-MIBI group. Evan blue infusion during ischemia and TTC staining after operation were used to delineate the area of ischemic and viable myocardium. The isolated heart was sliced in the short axis and then autoradiography was performed. The electron microscopic examination was also done for the myocardial samples. 99Tc(m)-HL91 and 99Tc(m)-MIBI uptake activities (counts/g) were measured in the area of ischemic myocardium (T) and normal myocardium (NT) separately. The uptake ratios of 99Tc(m)-HL91 and that of 99Tc(m)-MIBI in ischemic myocardium were calculated as T/NT. It was found that the normal myocardium was blue and ischemic or infarct myocardium was negative with Evans blue in all experiment rats. Both the normal and ischemic myocardium was in red color with TTC staining. In the 99Tc(m)-HL91 group the ischemic myocardium showed much higher uptake over normal myocardium, that was demonstrated both in the autoradiography and quantitative analysis. The ischemic/normal activity ratios were 1.634 +/- 0.354. It was suggested that 99Tc(m)-HL91 might accumulate in ischemic and viable myocardium, which is helpful in the evaluation of hypoxic but viable myocardium and potentially used as a imaging agent to assess myocardial viability. PMID:16961269

  7. Salusins protect myocardium against ischemic injury by alleviating endoplasmic reticulum stress.

    PubMed

    Wang, Jianfei; Wang, Yin; Shan, Shifu; Hu, Tiantian; Chen, Huyan; Tian, Jing; Ren, Anjing; Zhou, Xu; Yuan, Wenjun; Lin, Li

    2012-04-01

    Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-α and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery (LAD), salusin-α or -β was intravenously injected at 5 or 15 nmol kg(-1) 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD occlusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg(-1) salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the activation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP (C/EBP homologous protein), and attenuated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myocardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis. PMID:22566093

  8. Pioglitazone increases PGC1-α signaling within chronically ischemic myocardium.

    PubMed

    Butterick, Tammy A; Hocum Stone, Laura; Duffy, Cayla; Holley, Christopher; Cabrera, Jesús A; Crampton, Melanie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

    2016-05-01

    The peroxisome proliferator-activated receptor (PPAR)-γ drug pioglitazone (PIO) has been shown to protect tissue against oxidant stress. In a swine model of chronic myocardial ischemia, we tested whether PIO increases PGC1-α signaling and the expression of mitochondrial antioxidant peptides. Eighteen pigs underwent a thoracotomy with placement of a fixed constrictor around the LAD artery. At 8 weeks, diet was supplemented with either PIO (3 mg/kg) or placebo for 4 weeks. Regional myocardial function and blood flow were determined at the time of the terminal study. PGC1-α expression was quantified from nuclear membranes by gels and respiration, oxidant stress markers and proteomics by iTRAQ were determined from isolated mitochondria. In the chronically ischemic LAD region, wall thickening from the PIO and control groups was 42 ± 6 and 45 ± 5 %, respectively (NS) with no intergroup differences in basal blood flow (0.72 ± 0.04 versus 0.74 ± 0.04 ml/min g, respectively; NS). In the PIO group, the expression of nuclear bound PGC1-α was higher (11.3 ± 2.6 versus 4.4 ± 1.4 AU; P < 0.05) and the content of mitochondrial antioxidant peptides including superoxide dismutase 2, aldose reductase, glutathione S-transferase and thioredoxin reductase were greater than controls. Although isolated mitochondria from the PIO group showed lower state 3 respiration (102 ± 13 versus 161 ± 22 nmol/min mg; P < 0.05), no differences in oxidant stress were noted by protein carbonyl (1.7 ± 0.7 versus 1.1 ± 0.1 nmol/mg). Chronic pioglitazone does not reduce regional myocardial blood flow or function in a swine model of chronic myocardial ischemia, but may have an important role in increasing expression of antioxidant proteins through PGC1-α signaling. PMID:27138931

  9. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

    PubMed Central

    Galagudza, Michael; Korolev, Dmitry; Postnov, Viktor; Naumisheva, Elena; Grigorova, Yulia; Uskov, Ivan; Shlyakhto, Eugene

    2012-01-01

    Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery. PMID:22619519

  10. Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine myocardium.

    PubMed

    Robitaille, P M; Rath, D P; Abduljalil, A M; O'Donnell, J M; Jiang, Z; Zhang, H; Hamlin, R L

    1993-12-15

    Oxidative metabolism in the in vivo canine myocardium was studied noninvasively using 13C-enriched acetate and non-steady state 13C NMR techniques. Under low workload conditions, the myocardium oxidized the infused [2-13C]acetate and incorporated the labeled carbon into the glutamate pool as expected. This conclusion stems from the rapid enrichment of the C-2, C-3, and C-4 carbons of glutamic acid both under in vivo conditions and in extracts. Surprisingly, [2-13C]acetate uptake was not observed at high workloads as reflected by an absence of glutamate pool enrichment at these rate pressure products. Rather, the myocardium selected its substrate from an endogenous pool. Since free acetate can directly cross the inner mitochondrial membrane and be converted to acetyl-CoA through acetyl-CoA synthetase, these results support workload-dependent regulation of substrate access to the mitochondrial CoASH pool. As such, we advance the hypothesis that the selection of substrate for condensation with CoASH and subsequent oxidation in the tricarboxylic acid cycle is regulated kinetically through the Km values of the appropriate condensation enzymes and through the absolute levels of free CoASH in the mitochondria. PMID:8253751

  11. Molecular Imaging of Induced Pluripotent Stem Cell Immunogenicity with In Vivo Development in Ischemic Myocardium

    PubMed Central

    Wang, Haibin; Zhou, Jin; Zhao, Mengge; Lin, Qiuxia; Wang, Yan; Li, Junjie; Li, Dexue; Du, Zhiyan; Yao, Anning; Cao, Feng; Wang, Changyong

    2013-01-01

    Whether differentiation of induced pluripotent stem cells (iPSCs) in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection, is unclear. Here, we dynamically demonstrated the immunogenicity and rejection of iPSCs in ischemic myocardium using bioluminescent imaging (BLI). Murine iPSCs were transduced with a tri-fusion (TF) reporter gene consisting of firefly luciferase-red fluorescent protein-truncated thymidine kinase (fluc-mrfp-tTK). Ascorbic acid (Vc) were used to induce iPSCs to differentiate into cardiomyocytes (CM). iPSCs and iPS-CMs were intramyocardially injected into immunocompetent or immunosuppressed allogenic murine with myocardial infarction. BLI was performed to track transplanted cells. Immune cell infiltration was evaluated by immunohistochemistry. Syngeneic iPSCs were also injected and evaluated. The results demonstrated that undifferentiated iPSCs survived and proliferated in allogenic immunocompetent recipients early post-transplantation, accompanying with mild immune cell infiltration. With in vivo differentiation, a progressive immune cell infiltration could be detected. While transplantation of allogenic iPSC-CMs were observed an acute rejection from receipts. In immune-suppressed recipients, the proliferation of iPSCs could be maintained and intramyocardial teratomas were formed. Transplantation of syngeneic iPSCs and iPSC-CMs were also observed progressive immune cell infiltration. This study demonstrated that iPSC immunogenicity increases with in vivo differentiation, which will increase their chance for rejection in iPSC-based therapy. PMID:23840453

  12. Coronary arteries angiogenesis in ischemic myocardium: biocompatibility and biodegradability of various hydrogels.

    PubMed

    Shen, Xiaodong; Tanaka, Kuniyoshi; Takamori, Atsushi

    2009-10-01

    To evaluate the biocompatibility and biodegradability of various hydrogels and choose suitable hydrogels for the coronary arteries angiogenesis in ischemic myocardium, we synthesized six kinds of hyaluronan hydrogels, fibrin hydrogel, poly(vinyl alcohol)-chitosan hydrogel, and obtained elastin hydrogels. We examined their degradation rates and cytotoxicity in vitro. Then, hydrogels were implanted into rat adductor muscles for 1, 2, or 4 weeks. Hydrogels and surrounding tissues were resected, followed by hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemical staining for measurements of degradation, immune response, and angiogenesis. 2-Iminothiolane grafted hyaluronan hydrogel and periodate oxidated hyaluronan hydrogel presented rapid degradation rates, low quantity of inflammation-mediating cells (12 +/- 3 and 12 +/- 4 per 2.5 x 10(-3) mm(2), respectively, at week 2), thin fibrous capsules (scores were 3.8 +/- 0.1 and 4.0 +/- 0.3 per 0.33 mm(2), respectively, at week 2) with dense blood vessels in the areas surrounding the implanted hydrogels. 2-Iminothiolane grafted hyaluronan and periodate oxidated hyaluronan hydrogels with appropriate degradation rates and low immune responses were suitable for coronary arteries angiogenesis in ischemic myocardium. PMID:19681839

  13. Ultrastructural and functional effects of lead poisoning on adult canine myocardium: assessment of thiamin treatment

    SciTech Connect

    Kincaid, N.G.

    1985-01-01

    The effects of lead (Pb) poisoning on the adult canine myocardium were assessed quantitatively using stereological techniques, functional testing, and blood analyses as well as qualitatively by morphological investigation. Relative measurements using stereological techniques compared the volume fractions of cellular components of the three groups. Blood was analyzed for lead, hemoglobin, hematocrit, total erythrocytes, total leukocytes, thiamin pyrophosphate (TPP), delta-aminolevulinic acid dehydratase activity (ALAD), and zinc protoporphyrin (ZPP). The major finding of the stereological analysis was the statistically significant increase of 3.2% in myofilament volume in the Pb treated group and the significant decrease in mitochondrial volume in both the Pb treated and Pb + B/sub 1/ treated groups. A statistically significant decrease in the mitochondria/myofilament volume ratio was found in the Pb treated, but no Pb + B/sub 1/ treated group. This may indicate either a protective effect of thiamin on mitochondria or a reduced compensatory need of the myocyte to increase myofilament volume.

  14. Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo

    PubMed Central

    Lei, Biao; Matsuo, Ken; Labinskyy, Volodymyr; Sharma, Naveen; Chandler, Margaret P.; Ahn, Anna; Hintze, Thomas H.; Stanley, William C.; Recchia, Fabio A.

    2005-01-01

    Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although the underlying mechanism(s) and functional consequences of this effect are not clearly understood. We tested the hypothesis that NO inhibits the activation of AMP-activated protein kinase (AMPK) and translocation of cardiac glucose transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced in open-chest dogs by a 66% flow reduction in the left anterior descending coronary artery (LAD). During ischemia, dogs were untreated (control) or treated by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 μg·kg–1·min–1); (ii) 8-Br-cGMP (50 μg·kg–1·min–1); or (iii) NO synthase inhibitor l-nitro-argininemethylester (40 μg·kg–1·min–1; n = 9 per group). Cardiac substrate oxidation was measured with isotopic tracers. There were no differences in myocardial blood flow or oxygen delivery among groups; however, at 45 min of ischemia, the activation of AMPK was significantly less in NTG (77 ± 12% vs. nonischemic myocardium) and 8-Br-cGMP (104 ± 13%), compared with control (167 ± 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 ± 7%) and 8-Br-cGMP (120 ± 11%), compared with control (165 ± 17%). Glucose uptake and lactate output were 30% and 60% lower in NTG compared with control. Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and glucose uptake. Contractile function in the ischemic region was significantly improved by NTG and l-nitro-argininemethylester. In conclusion, in ischemic myocardium an NO donor inhibits glucose uptake and lactate production via a reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of metabolic modulation and myocardial protection activated by NO donors. PMID:15870202

  15. The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury

    PubMed Central

    2013-01-01

    Background MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. Methods 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. Results Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p = 0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p = 0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r = 0.469, p < 0.001 and r = 0.273, p = 0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. Conclusion Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery. PMID:23800236

  16. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    SciTech Connect

    Waksman, Ron; Baffour, Richard

    2003-09-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

  17. Study of possible mechanism of protective effect of phosphocreatine on ischemic myocardium

    SciTech Connect

    Preobrazhenskii, A.N.; Dzhavadov, S.A.; Saks, V.A.

    1986-10-20

    The accumulation of (/sup 32/P)phosphocreatine by control and isolated perfused ischemic rat hearts was studied. It was found that at phosphocreatine concentrations of 0.5-10 mM in the perfusing solution the rate of phosphocreatine accumulation was twice as high in hearts subjected to ischemia for 35 min as in the control hearts and constituted 182 nmoles/min/g dry weight tissue at a phosphocreatine concentrations in the perfusate of 10 mM. 5'-Nucleotidase and phosphatase activities were found in the crude plasma membrane fraction from rat hearts. The pH-dependence of the activity of these enzymes was studied. The 5'-nucleotidase activity decreased 4- to 5-fold with a drop in the pH from 8.0 to 6.0. The phosphatase activity of the preparations increased 2-fold with a drop in the pH from 8.0 to 6.0. The 5'-nucleotidase activity was inhibited by 10 mM phosphocreatine in the presence of 5 mM Mg/sup 2 +/, and the degree of the inhibition depended on the pH. Maximum inhibition by phosphocreatine (58%) was observed at pH 6.0. The inhibition of phosphatase by phosphocreatine did not depend on the pH and reached 20% in the presence of 10 mM phosphocreatine. Some possible mechanisms of the protective effect of phosphocreatine on an ischemic myocardium are discussed.

  18. A conducting salt-based amperometric biosensor for measurement of extracellular lactate accumulation in ischemic myocardium.

    PubMed

    Marzouk, S A; Cosofret, V V; Buck, R P; Yang, H; Cascio, W E; Hassen, S S

    1997-07-15

    In this paper, fabrication, characterization, and physiological application of a miniaturized amperometric lactate biosensor are described. The sensor is based on cross-linked lactate oxidase and tetrathiafulvalene-tetracyano-quinodimethane (TTF-TCNQ) charge transfer complex. The sensor was developed for continuous quantitative measurement of the lactate accumulation in ischemic myocardium under severe depletion of oxygen. The sensor was evaluated in vitro at an applied potential of 0.15 V vs Ag/AgCl; it proved to combine all the performance characteristics desired for the present application, such as proper response in absence of oxygen, good operational stability, good accuracy and precision (103.5 +/- 1.2%), adequate response time (t95% = 80 s), and wide linear dynamic range up to 27 mM (r = 0.9998) in N2-saturated solutions and at 37 degrees C. The prepared sensors (n = 12) showed sensitivity of 380 +/- 90 nA/mM, and a background current of 240 +/- 50 nA. The lower limit of detection is 0.4 +/- 0.15 mM with a S/N ratio equal to 3. Results obtained for direct lactate monitoring in ischemic rabbit papillary muscle under no-flow conditions and PO2 < 6 mm Hg are presented. PMID:9230678

  19. Alteration of gene expression for glycolytic enzymes in aerobic and ischemic myocardium.

    PubMed

    Liedtke, A J; Lynch, M L

    1999-10-01

    The purpose of this report was to describe mRNA abundance for the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and pyruvate dehydrogenase in ischemic and adjacent aerobic myocardium. Mechanical, metabolic, and mRNA data were acquired in a pig model of regulated coronary flow using extracorporeal perfusion. Trials of coronary hypoperfusion included sustained and intermittent exposures of acute ischemia with or without reperfusion. These were compared with a chronic 4-day model of partial coronary stenosis. In ischemic tissues, levels of mRNA, normalized by mRNA for beta-actin, were increased over control values for GAPDH (range 2.7- to 4.6-fold), pyruvate kinase (2.9-fold), and pyruvate dehydrogenase (2.1-fold). It is of interest that increases in mRNA levels over control values were also observed in adjacent aerobic heart muscle from intervention hearts, including 3.6- to 4.5-fold elevations in message for GAPDH and a 2.1-fold increase in signal for pyruvate dehydrogenase. Augmentation in mRNA abundance occurred in as short a time as 40 min of ischemia and was maintained for as long as 4 days in partial coronary stenosis. Whether the former time was of an interval sufficient to affect protein production is problematic, but the latter time was ample to influence enzyme concentration, which may in turn have regulated glycolysis in this condition. PMID:10516179

  20. Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

    PubMed Central

    Wang, LiNa; Yao, ChunXia; Wu, Fei; Lin, Xiao; Shen, Lan; Feng, Yi

    2015-01-01

    Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P20k-R), 40-kDa PEG mono-modified ROP (P40k-R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P40k-R. With regard to P20k-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P40k-R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects. PMID:26425081

  1. Postischemic cardiac recovery in heme oxygenase-1 transgenic ischemic/reperfused mouse myocardium

    PubMed Central

    Juhasz, Bela; Varga, Balazs; Czompa, Attila; Bak, Istvan; Lekli, Istvan; Gesztelyi, Rudolf; Zsuga, Judit; Kemeny-Beke, Adam; Antal, Miklos; Szendrei, Levente; Tosaki, Arpad

    2011-01-01

    Abstract Heme oxygenase-1 (HO-1) transgenic mice (Tg) were created using a rat HO-1 genomic transgene. Transgene expression was detected by RT-PCR and Western blots in the left ventricle (LV), right ventricle (RV) and septum (S) in mouse hearts, and its function was demonstrated by the elevated HO enzyme activity. Tg and non-transgenic (NTg) mouse hearts were isolated and subjected to ischemia/reperfusion. Significant post-ischemic recovery in coronary flow (CF), aortic flow (AF), aortic pressure (AOP) and first derivative of AOP (AOPdp/dt) were detected in the HO-1 Tg group compared to the NTg values. In HO-1 Tg hearts treated with 50 μmol/kg of tin protoporphyrin IX (SnPPIX), an HO enzyme inhibitor, abolished the post-ischemic cardiac recovery. HO-1 related carbon monoxide (CO) production was detected in NTg, HO-1 Tg and HO-1 Tg + SnPPIX treated groups, and a substantial increase in CO production was observed in the HO-1 Tg hearts subjected to ischemia/reperfusion. Moreover, in ischemia/reperfusion-induced tissue Na+ and Ca2+ gains were reduced in HO-1 Tg group in comparison with the NTg and HO-1 Tg + SnPPIX treated groups; furthermore K+ loss was reduced in the HO-1 Tg group. The infarct size was markedly reduced from its NTg control value of 37 ± 4% to 20 ± 6% (P < 0.05) in the HO-1 Tg group, and was increased to 47 ± 5% (P < 0.05) in the HO-1 knockout (KO) hearts. Parallel to the infarct size reduction, the incidence of total and sustained ventricular fibrillation were also reduced from their NTg control values of 92% and 83% to 25% (P < 0.05) and 8% (P < 0.05) in the HO-1 Tg group, and were increased to 100% and 100% in HO-1 KO−/− hearts. Immunohistochemical staining of HO-1 was intensified in HO-1 Tg compared to the NTg myocardium. Thus, the HO-1 Tg mouse model suggests a valuable therapeutic approach in the treatment of ischemic myocardium. PMID:20716121

  2. Coenzyme Q10 protects ischemic myocardium in an open-chest swine model.

    PubMed

    Atar, D; Mortensen, S A; Flachs, H; Herzog, W R

    1993-01-01

    Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism. PMID:8241692

  3. Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium.

    PubMed

    Costa, K D; Takayama, Y; McCulloch, A D; Covell, J W

    1999-02-01

    Previous studies suggest that the laminar architecture of left ventricular myocardium may be critical for normal ventricular mechanics. However, systolic three-dimensional deformation of the laminae has never been measured. Therefore, end-systolic finite strains relative to end diastole, from biplane radiography of transmural markers near the apex and base of the anesthetized open-chest canine anterior left ventricular free wall (n = 6), were referred to three-dimensional laminar microstructural axes reconstructed from histology. Whereas fiber shortening was uniform [-0.07 +/- 0.04 (SD)], radial wall thickening increased from base (0. 10 +/- 0.09) to apex (0.14 +/- 0.13). Extension of the laminae transverse to the muscle fibers also increased from base (0.08 +/- 0. 07) to apex (0.11 +/- 0.08), and interlaminar shear changed sign [0. 05 +/- 0.07 (base) and -0.07 +/- 0.09 (apex)], reflecting variations in laminar architecture. Nevertheless, the apex and base were similar in that at each site laminar extension and shear contributed approximately 60 and 40%, respectively, of mean transmural thickening. Kinematic considerations suggest that these dual wall-thickening mechanisms may have distinct ultrastructural origins. PMID:9950861

  4. Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

    PubMed Central

    Willerson, James T.; Powell, Wm. John; Guiney, Timothy E.; Stark, James J.; Sanders, Charles A.; Leaf, Alexander

    1972-01-01

    The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery. Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005). Thus, increases in serum osmolality produced by mannitol result in the following beneficial changes during myocardial ischemia: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow. PMID:4640943

  5. Recovery of glucose metabolism in reperfused canine myocardium demonstrated by positron-CT (PCT)

    SciTech Connect

    Schwaiger, M.; Sochor, H.; Parodi, O.; Grover, M.; Hansen, H.W.; Selin, C.; Schelbert, H.R.

    1984-01-01

    The authors previously examined with PCT in chronic dogs the long term metabolic recovery during reperfusion after a 3 hr ischemic insult. Increased regional glucose utilization at 24 hrs of R accurately identified reversible tissue injury documented by late improvement in segmental function by ultrasonic crystals. To define the early metabolic events after a 3 hr LAD balloon occlusion, regional blood flow and glucose utilization was studied in 8 dogs with PCT, N-13 ammonia (NA) and F-18 deoxyglucose (FDG) at 2 hrs and at 24 hrs after R. The dogs were then thoracotomized and MBF by microspheres, arterio-venous differences for glucose, lactate and O/sub 2/ across the reperfused segment (LAD vein) and the left ventricle (coronary sinus) measured. Immediately after reperfusion, MBF and FDG uptake were 27 +- 24% and 21 +- 48% lower in the reperfused territory (RT) than in control myocardium (C). At 24 hrs, MBF by microspheres was and 22 +- 25% lower and FDG uptake 175 +- 73% higher in RT than in C. In the RT, consumption of glucose (by Fick method) was 202 +- 107% higher, of lactate 96 +- 85% lower and of O/sub 2/ 42 +- 26% lower than in the entire LV. PCT measured FDG uptake correlated with glucose consumption (r=0.94) and confirmed that the segmentally increased FDG uptake at 24 hrs reflected increased glucose utilization that, as indicated by the reduced lactate consumption, was partly anaerobic. The authors conclude that initially after R, glucose metabolism is depressed but increases above C within 24 hrs, a time course that now can be determined noninvasively with PCT and is useful for predicting functional recovery.

  6. Investigating the Effects of Resveratrol on Chronically Ischemic Myocardium in a Swine Model of Metabolic Syndrome: A Proteomics Analysis

    PubMed Central

    Sabe, Ashraf A.; Sadek, Ahmed A.; Elmadhun, Nassrene Y.; Dalal, Rahul S.; Robich, Michael P.; Bianchi, Cesario

    2015-01-01

    Abstract Resveratrol has been shown to improve cardiac perfusion and ventricular function after chronic ischemic injury. Using proteomic analysis, we sought to objectively investigate potential mechanisms, by which resveratrol exerts its cardioprotective effects in the setting of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were divided into two groups based on diet: high cholesterol (n=7) or a high-cholesterol diet with supplemental resveratrol (n=6). Four weeks later, all animals underwent surgical placement of an ameroid constrictor to their left circumflex artery. Diets were continued for another 7 weeks, and then the ischemic myocardium was harvested for proteomics analysis. Proteomic analysis identified 669 common proteins between the two groups. Of these proteins, 76 were statistically different, of which 41 were characterized (P<.05). Pathway analysis demonstrated that in animals supplemented with resveratrol, there was a downregulation in several proteins involved with mitochondrial dysfunction, cell death, and unfavorable cardiac remodeling. Furthermore, there was an upregulation in proteins involved in free radical elimination. We conclude that resveratrol supplementation significantly alters several critical protein markers in the chronically ischemic myocardium. Further investigation of these proteins may help elucidate the mechanisms by which resveratrol exerts its cardioprotective effects. PMID:25089828

  7. Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

    PubMed Central

    Ashton, Kevin J.; Tupicoff, Amanda; Williams-Pritchard, Grant; Kiessling, Can J.; See Hoe, Louise E.; Headrick, John P.; Peart, Jason N.

    2013-01-01

    Background Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. Conclusions Protection via SLP is associated with transcriptional repression of inflammation/immunity, up

  8. Effect of diltiazem on stunned myocardium evaluated with 99mTc-pyrophosphate imaging in canine heart.

    PubMed

    Nohara, R; Kambara, H; Okuda, K; Ono, S; Tamaki, N; Konishi, J; Kawai, C

    1992-03-01

    The effect of diltiazem on stunned myocardium was evaluated by measuring the myocardial uptake of 99mTc-PYP (pyrophosphate) in open chest experiments with dogs. Myocardial stunning was induced by a 30 min ischemic occlusion of the anterior descending coronary artery. Regional wall motion was monitored by echocardiography of the epicardium for 2 h during reperfusion. After a 30 min occlusion of the coronary artery, it was reperfused and 99mTc-PYP was injected, followed by 201Tl 2 h later. The ischemic area was defined by Evans blue dye, and the infarct area by TTC staining. No dogs showed infarcts or 201Tl defects in this study group. Five dogs of the control-1 group (C1, ischemic area = 19.1 +/- 3.2%) showed decreased regional wall motion during occlusion (15.5 +/- 3.5% of control), and a slow recovery from depressed motion after 2 h of reperfusion (20.3 +/- 9.3%) with uptake ratio (compared to the non-ischemic area uptake) of 99mTc-PYP (4.96 +/- 2.28). In contrast, both groups with diltiazem infusion (20 micrograms/kg/min), started either 30 min before ischemia (D1 = 5 dogs) or just after reperfusion (D2 = 5 dogs), showed significantly better recovery after 2 h of reperfusion (D1:115.4 +/- 36.0%, D2:109.2 +/- 44.2%) than C1 (p less than 0.05), D1 and D2 groups also showed suppressed 99mTc-PYP uptake ratio (D1:1.06 +/- 0.33, D2:2.34 +/- 2.05, p less than 0.05 vs C1) in spite of comparable ischemic area. Four dogs with small ischemic area (C2:5.3 +/- 5.0%) did not show increased 99mTc-PYP uptake (1.15 +/- 0.35), and regional wall motion after 2 h of reperfusion was 96.1 +/- 24.1% of the control value (p less than 0.05 vs C1). Thus, diltiazem was effective in enhancing the suppression of 99mTc-PYP uptake in the stunned myocardium, and similar results were obtained for small ischemic areas. The protective effect of diltiazem appears to be strongly related to the mechanism of 99mTc-PYP uptake. PMID:1532431

  9. Toll-like Receptor 4 Mediates the Inflammatory Responses and Matrix Protein Remodeling in Remote Non-Ischemic Myocardium in a Mouse Model of Myocardial Ischemia and Reperfusion

    PubMed Central

    Zhai, Yufeng; Ao, Lihua; Cleveland, Joseph C.; Zeng, Qingchun; Reece, T. Brett; Fullerton, David A.; Meng, Xianzhong

    2015-01-01

    The signaling mechanism that mediates inflammatory responses in remote non-ischemic myocardium following regional ischemia/reperfusion (I/R) remains incompletely understood. Myocardial Toll-like receptor 4 (TLR4) can be activated by multiple proteins released from injured cells and plays a role in myocardial inflammation and injury expansion. We tested the hypothesis that TLR4 occupies an important role in mediating the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional I/R injury. Methods and results: TLR4-defective (C3H/HeJ) and TLR4-competent (C3H/HeN) mice were subjected to coronary artery ligation (30 min) and reperfusion for 1, 3, 7 or 14 days. In TLR4-competent mice, levels of monocyte chemoattractant protein -1 (MCP-1), keratinocyte chemoattractant (KC), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were elevated in the remote non-ischemic myocardium at day 1, 3, and 7 of reperfusion. Levels of collagen I, collagen IV, matrix metalloproteinase (MMP) 2 and MMP 9 were increased in the remote non-ischemic myocardium at day 7 and 14 of reperfusion. MMP 2 and MMP 9 activities were also increased. TLR4 deficiency resulted in a moderate reduction in myocardial infarct size. However, it markedly downgraded the changes in the levels of chemokines, adhesion molecules and matrix proteins in the remote non-ischemic myocardium. Further, left ventricular function at day 14 was significantly improved in TLR4-defective mice. In conclusion, TLR4 mediates the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional myocardial I/R injury and contributes to the mechanism of adverse cardiac remodeling. PMID:25823011

  10. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

    PubMed

    Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

    2011-11-01

    Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke. PMID:21673716

  11. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy

    PubMed Central

    Zhang, Xiaoli; Schindler, Thomas H.; Prior, John O.; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng

    2016-01-01

    Purpose The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Methods Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25±10 %) were studied with 13N-ammonia and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to 13N-ammonia activity ratios. Results Rest MBF was reduced in viable (0.42±0.18 ml/min per g) and nonviable regions (0.32±0.09 ml/min per g) relative to remote regions (0.68±0.23 ml/min per g, p<0.001) and to normals (0.63±0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p<0.05) and stress (p<0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p>0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39±0.56 vs 1.70±0.45, p>0.05) but were significantly lower in nonviable regions (1.23±0.43, p<0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40±0.14 vs 0.90±0.20, p<0.001) and in nonviable regions (1.13±0.21, p<0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r=−0.424, p<0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. Conclusion As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes. PMID:23287994

  12. Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway.

    PubMed

    Xu, Guang; Takashi, En; Kudo, Mitsuhiro; Ishiwata, Toshiyuki; Naito, Zenya

    2004-02-01

    Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction, there is disagreement about the sensitivity of ischemic injury of an infarcted myocardium in experimental studies. The present study evaluated the influences of different durations of hyperglycemia on ischemic and reperfusion injuries of the myocardium, and focused on extracellular signal-regulated kinase 1/2 (ERK1/2), which plays an important role in the intracellular signaling pathway and is reported to be associated with myocardial protection against heart injury. Short- and long-term hyperglycemias were induced in rats by streptozotocin (STZ) injection and the rats were examined 4 (4WDM) and 20 weeks (20WDM) after the treatment. Ischemia and reperfusion were induced by occlusion and reperfusion (I/R) of the left coronary artery (LCA). I/R-induced infarct size was determined using triphenyltetrazolium chloride (TTC) staining. After 20 weeks of STZ treatment (20WDM+I/R), the infarct size in the rat heart increased by 65.2 +/- 4.3%, whereas after 4 weeks of STZ treatment (4WDM+I/R), the infarct size decreased compared with the time-matched I/R group (43.1 +/- 3.6% and 59.5 +/- 5.6%, respectively). The number of dead myocytes including necrotic and apoptotic cells was determined using horseradish peroxidase (HRP) and terminal deoxynucleotide nick-end labeling (TUNEL) methods. The number of dead myocytes decreased in the 4WDM+I/R group, while the number of dead myocytes increased markedly in the 20WDM+I/R group, compared with the time-matched I/R group. The increment of ERK1/2 phosphorylation in the 4WDM group and the slight enhancement of this phosphorylation by I/R treatment were observed by western blotting. However, in the 20WDM group, the level of ERK1/2 phosphorylation reduced by approximately 1/3 compared with the time-matched control group; moreover, I/R treatment did not enhance the phosphorylation level. This study demonstrated that short- and long

  13. Fluorescence lifetime measurements of NADH and tryptophan in intact ischemic, intact rabbit myocardium

    NASA Astrophysics Data System (ADS)

    Hamburger, Adrian; Gryczynski, Zygmunt; Lakowicz, Joseph R.; Sommers, Keith

    1999-07-01

    Ischemia-reperfusion injury is the leading cause of early dysfunction following transplantation. Currently, there are no techniques available to accurately measure ischemic changes during organ storage. Therefore, the interest exists in developing non-invasive monitoring techniques. We used NADH and tryptophan as fluorescent markers, since both are intrinsic fluorophores and excellent indicators for levels of hypoxia and protein denaturation, respectively.

  14. Intrinsic washout rates of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation

    SciTech Connect

    Beller, G.A.; Holzgrefe, H.H.; Watson, D.D.

    1985-02-01

    Infusion of dipyridamole has been suggested as an alternative to exercise stress for myocardial perfusion imaging for detection of ischemia, but the mechanism and significance of thallium-201 (/sup 201/Tl) redistribution after administration of dipyridamole are uncertain. If disparate intrinsic cellular efflux rates of /sup 201/Tl from normal and relatively underperfused myocardium in response to dipyridamole-induced vasodilation were observed, this could explain delayed /sup 201/Tl redistribution. We investigated the effect of an intravenous infusion of 0.15 mg/kg dipyridamole on the intrinsic myocardial washout rate of /sup 201/Tl as measured with a gamma-detector probe after intracoronary injection (50 muCi) of the radionuclide in open-chested anesthetized dogs. In six normal dogs the t 1/2 for intrinsic /sup 201/Tl washout from the myocardium was 89 +/- 11 min (SE) at control conditions and became more rapid at 59 +/- 10 min (p . .0001) after dipyridamole. This corresponded to a significant increase in microsphere-determined epicardial (0.95 +/- 0.11 to 2.23 +/- 0.46 ml/min/g; p . .01) and endocardial (0.86 +/- 0.10 to 1.53 +/- 0.27; p . .029) flows. In 12 dogs with a critical coronary stenosis, the /sup 201/Tl intrinsic washout rate slowed from 70 +/- 5 to 104 +/- 6 min (p . .0001) after production of the stenosis and slowed even further to 169 +/- 21 min (p . .003) after dipyridamole.

  15. Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents

    PubMed Central

    Liu, Alexander; Wijesurendra, Rohan S.; Francis, Jane M.; Robson, Matthew D.; Neubauer, Stefan; Piechnik, Stefan K.; Ferreira, Vanessa M.

    2016-01-01

    Objectives The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. Background In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Methods Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Results Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 ± 19 ms at 1.5-T; 1,189 ± 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 ± 0.5% at 1.5-T; 6.3 ± 1.1% at 3.0-T; all p < 0.0001). Infarcted myocardium showed the highest resting T1 of all tissue classes (1,442 ± 84 ms), without significant T1 reactivity (0.2 ± 1.5%). Ischemic myocardium showed elevated resting T1 compared to normal (987 ± 17 ms; p < 0.001) without significant T1 reactivity (0.2 ± 0.8%). Remote myocardium, although having comparable resting T1 to normal (955 ± 17 ms

  16. Modulation of ephrinB2 leads to increased angiogenesis in ischemic myocardium and endothelial cell proliferation

    SciTech Connect

    Mansson-Broberg, Agneta; Siddiqui, Anwar J.; Genander, Maria; Grinnemo, Karl-Henrik; Hao Xiaojin; Andersson, Agneta B.; Waerdell, Eva; Sylven, Christer Corbascio, Matthias

    2008-08-29

    Eph/ephrin signaling is pivotal in prenatal angiogenesis while its potential role in postnatal angiogenesis largely remains to be explored. Therefore its putative angiogenic and therapeutic effects were explored in endothelium and in myocardial ischemia. In culture of human aortic endothelial cells the fusion protein ephrinB2-Fc induced cell proliferation (p < 0.0005) and in the murine aortic ring model ephrinB2-Fc induced increased sprouting (p < 0.05). Myocardial infarction was induced by ligation of the left anterior descending artery in mouse. During the following 2 weeks mRNA of the receptor/ligand pair EphB4/ephrinB2 was expressed dichotomously (p < 0.05) and other Eph/ephrin pairs were expressed to a lesser degree. Twenty-four hours after intraperitoneal administration of ephrinB2-Fc it was detected in abundance throughout the myocardium along capillaries, showing signs of increased mitosis. After 4 weeks the capillary density was increased 28% in the periinfarcted area (p < 0.05) to a level not different from healthy regions of the heart where no change was observed. These results implicate that EphB4/ephrinB2 is an important signaling pathway in ischemic heart disease and its modulation may induce therapeutic angiogenesis.

  17. Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography

    SciTech Connect

    Marwick, T.H.; MacIntyre, W.J.; Salcedo, E.E.; Go, R.T.; Saha, G.; Beachler, A. )

    1991-02-01

    The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. Increased post-exercise FDG uptake, appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization.

  18. Kinetics of a putative hypoxic tissue marker, Technetium-99m-nitroimidazole (BMS181321), in normoxic, hypoxic, ischemic and stunned myocardium

    SciTech Connect

    Kusuoka, Hideo; Hashimoto, Katsuji; Fukuchi, Kazuki

    1994-08-01

    This study focused on the kinetics of the newly developed {sup 99m}TTc-nitroimidazole, propyleneamine oxime-1,2-nitroimidazole (BMS181321) in the different setting of myocardial perfusion states and oxygenation levels, and compared the kinetics of BMS181321 with those of other technetium analogues. The kinetics of BMS181321 were evaluated in isolated perfused rat hearts. Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and a non-nitroimidazole-containing analogue of BMS 181321 (6-methyl propyleneamine oxime; PAO-6-Me) were used to compare their kinetics with those of BMS181321. BMS181321 cleared quickly from normoxic hearts and the retention in the myocardium 10 min after injection was 0.84% {plus_minus} 0.04% ID/g wet wt (mean {plus_minus} s.e.m.). In contrast, BMS181321 was retained after reperfusion when it was injected before ischemia; the uptake in the myocardium 10 min after reperfusion was significantly greater than in controls (23.9% {plus_minus} 3.9%ID/g wt, p<0.05). These results indicate that {sup 99m}Tc-BMS181321 is well trapped in ischemic myocardium and moderately trapped in hypoxic myocardium, but washed out quickly in stunned myocardium. The residence time influences the amount retained. 14 refs., 7 figs., 1 tab.

  19. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  20. Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.

    PubMed Central

    Frazier, D W; Wolf, P D; Wharton, J M; Tang, A S; Smith, W M; Ideker, R E

    1989-01-01

    The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period. Images PMID:2921316

  1. Myocardial kinetics of thallium-201 after stress in normal and perfusion-reduced canine myocardium

    SciTech Connect

    Okada, R.D.

    1985-12-01

    Despite the emerging use of quantitative computer programs for assessing myocardial thallium uptake and clearance after exercise, little is known about the kinetics of thallium after exercise stress. Accordingly, 11 mongrel dogs with experimental left anterior descending coronary stenoses were given thallium during norepinephrine infusion to simulate exercise. The infusion was discontinued and thallium activity was monitored regionally using miniature radiation detectors for 3 hours. Heart rate, arterial pressure and double product all increased significantly during norepinephrine infusion. The mean fractional myocardial thallium clearance was lower (0.47 +/- 0.03 (+/- standard error of the mean)) for the stenosis zone than for the no-stenosis zone (0.57 +/- 0.03) (p less than 0.0001). The stress blood flow ratio (stenosis/no-stenosis zone = 0.27 +/- 0.06) was significantly lower than the final thallium activity ratio (0.68 +/- 0.07) (p less than 0.001), consistent with thallium redistribution occurring over the 3-hour period. Myocardial thallium activity in the stenosis zone peaked in a mean of 2.2 minutes, then washed out biexponentially with a final decay constant of 0.0035 +/- 0.0005 min-1. Myocardial thallium activity in the no-stenosis zone peaked within 1 minute in all dogs, then washed out biexponentially, with a final decay constant of 0.0043 +/- 0.0003 (p less than 0.001 compared with stenosis zone). In conclusion, fractional clearance of thallium can differentiate myocardium distal to a coronary artery stenosis from that supplied by a normal coronary vessel.

  2. Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: role of NO.

    PubMed

    Asanuma, Hiroshi; Sanada, Shoji; Asakura, Masanori; Asano, Yoshihiro; Kim, Jiyoong; Shinozaki, Yoshiro; Mori, Hidezo; Minamino, Tetsuo; Takashima, Seiji; Kitakaze, Masafumi

    2014-08-01

    Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025-0.2 μg kg(-1) min(-1) into the canine coronary artery. A minimum dose of 0.1 μg kg(-1) min(-1) was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 μg kg(-1) min(-1), we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L(ω)-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts. PMID:24694647

  3. Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: Implications regarding the identification of myocardium at ischemic risk

    SciTech Connect

    Watters, T.A.; Botvinick, E.H.; Dae, M.W.; Cahalan, M.; Urbanowicz, J.; Benefiel, D.J.; Schiller, N.B.; Goldstone, G.; Reilly, L.; Stoney, R.J. )

    1991-07-01

    The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 (33%) of 15 vs. 1 (9%) of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed.

  4. Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium.

    PubMed

    Canan, Benjamin D; Haizlip, Kaylan M; Xu, Ying; Monasky, Michelle M; Hiranandani, Nitisha; Milani-Nejad, Nima; Varian, Kenneth D; Slabaugh, Jessica L; Schultz, Eric J; Fedorov, Vadim V; Billman, George E; Janssen, Paul M L

    2016-04-15

    It is well known that moderate exercise training elicits a small increase in ventricular mass (i.e., a physiological hypertrophy) that has many beneficial effects on overall cardiac health. It is also well known that, when a myocardial infarction damages part of the heart, the remaining myocardium remodels to compensate for the loss of viable functioning myocardium. The effects of exercise training, myocardial infarction (MI), and their interaction on the contractile performance of the myocardium itself remain largely to be determined. The present study investigated the contractile properties and kinetics of right ventricular myocardium isolated from sedentary and exercise trained (10-12 wk progressively increasing treadmill running, begun 4 wk after MI induction) dogs with and without a left ventricular myocardial infarction. Exercise training increased force development, whereas MI decreased force development that was not improved by exercise training. Contractile kinetics were significantly slower in the trained dogs, whereas this impact of training was less or no longer present after MI. Length-dependent activation, both evaluated on contractile force and kinetics, was similar in all four groups. The control exercise-trained group exhibited a more positive force-frequency relationship compared with the sedentary control group while both sedentary and trained post-MI dogs had a more negative relationship. Last, the impact of the β-adrenergic receptor agonist isoproterenol resulted in a similar increase in force and acceleration of contractile kinetics in all groups. Thus, exercise training increased developed force but slowed contractile kinetics in control (noninfarcted animals), actions that were attenuated or completely absent in post-MI dogs. PMID:26823341

  5. Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium*S⃞

    PubMed Central

    Chen, Chwen-Lih; Chen, Jingfeng; Rawale, Sharad; Varadharaj, Saradhadevi; Kaumaya, Pravin P. T.; Zweier, Jay L.; Chen, Yeong-Renn

    2008-01-01

    Increased \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document} and NO production is a key mechanism of mitochondrial dysfunction in myocardial ischemia/reperfusion injury. A crucial segment of the mitochondrial electron transport chain is succinate ubiquinone reductase (SQR or Complex II). In SQR, oxidative impairment and deglutathionylation of the 70-kDa flavin protein occurs in the post-ischemic heart (Chen, Y. R., Chen, C. L., Pfeiffer, D. R., and Zweier, J. L. (2007) J. Biol. Chem. 282,32640 -3265417848555). To gain insights into the oxidative modification of the 70-kDa protein in the post-ischemic myocardium, we used the identified S-glutathionylated peptide (77AAFGLSEAGFNTACVTK93) of the 70-kDa protein as a chimeric epitope incorporating a “promiscuous” T cell epitope to generate a high titer polyclonal antibody, AbGSC90. Purified AbGSC90 showed a high binding affinity to isolated SQR. Antibodies of AbGSC90 moderately inhibited the electron transfer and superoxide generation activities of SQR. To test for protein nitration, rats were subjected to 30 min of coronary ligation followed by 24 h of reperfusion. Tissue homogenates were immunoprecipitated with AbGSC90 and probed with antibodies against 3-nitrotyrosine. Enhancement of protein tyrosine nitration was detected in the post-ischemic myocardium. Isolated SQR was subjected to in vitro protein nitration with peroxynitrite, leading to site-specific nitration at the 70-kDa polypeptide and impairment of SQR electron transfer activity. Protein nitration of SQR further impaired its protein-protein interaction with Complex III. Liquid chromatography/tandem mass spectrometry analysis indicated that Tyr-56 and Tyr

  6. Dynamic 13C NMR analysis of pyruvate and lactate oxidation in the in vivo canine myocardium: evidence of reduced utilization with increased work.

    PubMed

    Rath, D P; Zhu, H; Tong, X; Jiang, Z; Hamlin, R L; Robitaille, P M

    1997-12-01

    In this work, substrate selection was monitored in the left ventricle of the canine myocardium by following pyruvate and lactate oxidation under in vivo conditions at basal and elevated workloads. These studies were conducted in the open chest model using dynamic 13C NMR techniques in the presence and absence of dichloroacetic acid (DCA), a well-known activator of pyruvate dehydrogenase (PDH). Following the infusion of (3-(13)C) pyruvate or (3-(13)C) lactate into the left anterior descending artery, highly variable 13C enrichments of glutamate, alanine, aspartate, and citrate were noted under low (RPP < 14,500 mmHg/min), intermediate (RPP = 15,000-25,000 mmHg/min), and high (RPP > 25,500 mmHg/min) rate pressure products (RPP). At low workloads, the myocardium typically oxidized the infused (3-(13)C) pyruvate or (3-(13)C) lactate and incorporated the labeled carbon into the glutamate pool as expected. However, in a few notable instances (n = 3), 13C-enriched pyruvate and lactate were unable to label the glutamate pool under in vivo conditions even at the lowest RPPs, indicating a lack of selection for these substrates by the tricarboxylic acid (TCA) cycle. Nonetheless, the levels of glutamate C4 enrichment observed at low workloads could usually be enhanced by infusion of DCA. Importantly, 13C NMR extract analysis revealed that (3-(13)C) pyruvate or (3-(13)C) lactate labeling of the glutamate pool was reduced (< 20%) at high workloads in spite of increased DCA concentrations. PMID:9402190

  7. No Evidence for Activated Autophagy in Left Ventricular Myocardium at Early Reperfusion with Protection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting

    PubMed Central

    Gedik, Nilgün; Thielmann, Matthias; Kottenberg, Eva; Peters, Jürgen; Jakob, Heinz; Heusch, Gerd; Kleinbongard, Petra

    2014-01-01

    Objective Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy. Methods CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation) or placebo (cuff deflated) before skin incision (n = 10/10). Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline) and at early (5–10 min) reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002). Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5–12 (ATG5-12) complex, light chain 3 (LC3), parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2)-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion. Results Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02). STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05). Conclusion Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion. PMID:24797938

  8. IL-8 up-regulates proliferative angiogenesis in ischemic myocardium in rabbits through phosphorylation of Akt/GSK-3βser9 dependent pathways

    PubMed Central

    Xie, Qiying; Sun, Zelin; Chen, Meifang; Zhong, Qiaoqing; Yang, Tianlun; Yi, Jun

    2015-01-01

    Background: Therapeutic myocardial angiogenesis is an important compensatory mechanism in severely coronary stenosis. Previous studies demonstrated that interleukin-8 (IL-8) not only plays an important role in inflammation, but also a potent angiogenic factor through p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-kappaB (NK-κB)-dependent pathway in carcinoma. Our study sought to investigate the effects of IL-8 on the angiogenesis and the underlying mechanism in the ischemic myocardium. Methods: Acute myocardial infarction animal model was established with male rabbits by directly suturing the left anterior descending branch, then lentivirus-mediated IL-8 was quarterly injected into the borderline of infarction area immediately. We employed CoCl2 induced hypoxic HUVECs for in vitro ischemia study. Left ventricular end-diastolic diameter (LVEDd) and ejection fraction (EF) were measured by echocardiography in pre-operation and at 6th week after operation. CD34 was detected with immunohistochemisty to analyse angiogenesis. Western blot was performed with regard to IL-8, protein kinase B (PKB/Akt) and Glycogen synthase kinase-3βser9 (GSK-3βser9). For the HUVECs’ proliferation and apoptosis, multiscan spectrum reader at A570 nm and annexin V-FITC/PI staining method were used respectively. Results: The levels of IL-8, phosphorylated Akt and GSK-3βser9 in focal myocardium significantly increased, and the over expression of IL-8 led to an increasing in angiogenesis in rabbits. Hypoxia inhibited cell proliferation and promoted apoptosis. IL-8 induced cell proliferation, phosphorylation of Akt and GSK-3βser9, inhibited apoptosis and Caspase3 expression in HUVECs, which were attenuated by anti-IL-8 or the Akt inhibitor LY294002. Conclusions: The present results indicate that IL-8 can increase angiogenesis in myocardial infarction, which maybe through enhancing Akt and GSK-3βser9 expression, and inhibiting myocardial apoptosis. PMID:26550160

  9. Exogenous hTERT gene transfected endothelial progenitor cells from bone marrow promoted angiogenesis in ischemic myocardium of rats

    PubMed Central

    Li, Shang-Hai; Wang, Dan-Dan; Xu, Yun-Jun; Ma, Guo-Dong; Li, Xing-Yue; Liang, Wei-Jun

    2015-01-01

    Objective: To explore the biological behavior and the revascularizative ability of endothelial progenitor cells (EPCs) transfected with human telomerase reverse transcriptase (hTERT) gene. Methods: EPCs were isolated from mononuclear cells in bone marrow by using the method of density gradient centrifugation, then cultured with differential velocity adherent method, EPCs were transfected by recombinant plasmid carrying GFP report gene EGFP-hTERT. The EPCs secretion and proliferation ability were detected before and after transfection. The expression of EPCs mRNA were detected by RT-PCR before and after transfection. The new capillaries of infarct area were observed. Results: After transgenesis, the proliferation of EPCs were increased, and the secretion of NO, LDH, iNOS by EPCs were significantly increased compared to the non-transgenesis group. After transplanted the transfected EPCs into the ischemic myocardial of rats, revascularization were increased obviously. Conclusion: EPCs maintained the original biological characteristics after transfecting exogenous hTER gene, the proliferation and survival rate were up-regulated significantly, and the revascularization ability of EPCs were significantly strengthen. PMID:26550433

  10. Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol

    PubMed Central

    Le, D. Elizabeth; Pascotto, Marco; Leong-Poi, Howard; Sari, Ibrahim; Micari, Antonio; Kaul, Sanjiv

    2013-01-01

    There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment endsystolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses

  11. Protective effect of pretreatment with the calcium antagonist anipamil on the ischemic-reperfused rat myocardium: a phosphorus-31 nuclear magnetic resonance study

    SciTech Connect

    Kirkels, J.H.; Ruigrok, T.J.; Van Echteld, C.J.; Meijler, F.L.

    1988-05-01

    To assess whether the prophylactic administration of anipamil, a new calcium antagonist, protects the heart against the effects of ischemia and reperfusion, rats were injected intraperitoneally twice daily for 5 days with 5 mg/kg body weight of this drug. The heart was then isolated and perfused by the Langendorff technique. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor myocardial energy metabolism and intracellular pH during control perfusion and 30 min of total ischemia (37/sup 0/C), followed by 30 min of reperfusion. Pretreatment with anipamil altered neither left ventricular developed pressure under normoxic conditions nor the rate and extent of depletion of adenosine triphosphate (ATP) and creatine phosphate during ischemia. Intracellular acidification, however, was attenuated. On reperfusion, hearts from anipamil-pretreated animals recovered significantly better than untreated hearts with respect to replenishment of ATP and creatine phosphate stores, restitution of low levels of intracellular inorganic phosphate and recovery of left ventricular function and coronary flow. Intracellular pH recovered rapidly to preischemic levels, whereas in untreated hearts a complex intracellular inorganic phosphate peak indicated the existence of areas of different pH within the myocardium. It is concluded that anipamil pretreatment protects the heart against some of the deleterious effects of ischemia and reperfusion. Because this protection occurred in the absence of a negative inotropic effect during normoxia, it cannot be attributed to an energy-sparing effect during ischemia. Therefore, alternative mechanisms of action are to be considered.

  12. Over-expression of HSPA12B protects mice against myocardium ischemic/reperfusion injury through a PPARγ-dependent PI3K/Akt/eNOS pathway

    PubMed Central

    Sun, Yanjun; Ye, Lincai; Jiang, Chuan; Jiang, Jun; Hong, Haifa; Qiu, Lisheng

    2015-01-01

    Acute myocardial ischemia/reperfusion (MIR) injury leads to severe arrhythmias and a high lethality. We aim to determine the effect of heat shock protein A12B (HSPA12B), a newly discovered member of the Hsp70 family, on heart injury parameters following MIR surgery. We used HSPA12B transgenic mice to determine its effects on heart function parameters, infarct size and cellular apoptosis following MIR surgery. Proinflammatory cytokines, oxidative products and anti-oxidative enzymes in the myocardium were measured to evaluate the anti-inflammatory and anti-oxidative effects of HSPA12B over-expression. The role of PPARs/eNOS/PI3k/Akt pathway was investigated using their inhibitors. The alteration of hemodynamic parameters, histopathological, apoptotic and infarct size caused by MIR was greatly attenuated in HSPA12B over-expressed mice. HSPA12B also greatly mitigated the inflammatory response, demonstrated by the decrease in the levels of IL-1β, IL-6, TNF-a and MPO. Anti-oxidative enzymes (SOD, Catalase and GPx) were restored by HSPA12B; oxidative products (8-OHdG, MDA and protein carbonyl) were decreased. HSPA12B activated the PPARγ-dependent eNOS/PI3k/Akt pathway, and the influence of HSPA12B on cardiac function was reversed by the inhibitors of eNOS, PPARγ, Akt and PI3K. Our results present a novel signaling mechanism that HSPA12B protects MIR injury through a PPARγ-dependent PI3K/Akt/eNOS pathway. PMID:26885270

  13. A quantitative index of regional blood flow in canine myocardium derived noninvasively with N-13 ammonia and dynamic positron emission tomography

    SciTech Connect

    Nienaber, C.A.; Ratib, O.; Gambhir, S.S.; Krivokapich, J.; Huang, S.C.; Phelps, M.E.; Schelbert, H.R. )

    1991-01-01

    To derive a quantitative index of regional myocardial blood flow, the arterial input function of the flow tracer N-13 ammonia and the regional myocardial N-13 activity concentrations were noninvasively determined in 29 experiments in eight dogs. N-13 ammonia was administered intravenously and cross-sectional images were acquired dynamically using an ECAT III positron emission tomograph with an effective in-plane resolution of 13.46 mm full-width half-maximum. Time-activity curves were derived from the serial images by assigning regions of interest to the left ventricular myocardium and left ventricular blood pool. Tracer net extractions were estimated from the myocardial time-activity concentrations at various times after tracer injection and the integral of the arterial input function. Myocardial blood flow was altered by intravenous dipyridamole, morphine, propranolol and partial or complete occlusion of the left anterior descending coronary artery, and ranged from 9 to 860 ml/min per 100 g. Estimates of tracer net extractions were most accurate when determined from the myocardial N-13 activity concentrations at 60 s divided by the integral of the arterial input function to that time. These estimates correlated with regional myocardial blood flows determined independently by the microsphere technique by y = x (1 - 0.64(e-114/x); SEE = 22.9; r = 0.94). First pass extraction fractions of N-13 ammonia determined noninvasively with this approach declined with higher flows in a nonlinear fashion and were similar to those determined invasively by direct intracoronary N-13 ammonia injections. The findings indicate that an accurate index of regional myocardial blood flow can be obtained noninvasively by high temporal sampling of arterial and myocardial tracer activity concentrations with positron emission tomography.

  14. MR Assessment of Myocardial Perfusion, Viability, and Function after Intramyocardial Transfer of VM202, a New Plasmid Human Hepatocyte Growth Factor in Ischemic Swine Myocardium1

    PubMed Central

    Saeed, Maythem; Martin, Alastair; Ursell, Phillip; Do, Loi; Bucknor, Matt; Higgins, Charles B.; Saloner, David

    2008-01-01

    Purpose: VM202, a newly constructed plasmid human hepatocyte growth factor, was transferred intramyocardially after infarction for the purpose of evaluating this strategy as a therapeutic approach for protection from left ventricular (LV) remodeling. Materials and Methods: The institutional animal care and use committee approved this study. Pigs underwent coronary artery occlusion and reperfusion and served as either control (n = 8) or VM202-treated (n = 8) animals. VM202 was transferred intramyocardially into four infarcted and four periinfarcted sites. Cardiac magnetic resonance (MR) imaging (cine, perfusion, delayed enhancement) was performed in acute (3 days) and chronic (50 days ± 3 [standard error of the mean]) infarction. Histopathologic findings were used to characterize and quantify neovascularization. The t test was utilized to compare treated and control groups and to assess changes over time. Results: In acute infarction, MR imaging estimates of function, perfusion, and viability showed no difference between the groups. In chronic infarction, however, VM202 increased maximum signal intensity and upslope at first-pass perfusion imaging and reduced infarct size at perfusion and delayed-enhancement imaging. These changes were associated with a decrease in end-diastolic (2.15 mL/kg ± 0.12 to 1.73 mL/kg ± 0.10, P < .01) and end-systolic (1.33 mL/kg ± 0.07 to 0.92 mL/kg ± 0.08, P < .001) volumes and an increase in ejection fraction (38.2% ± 1.3 to 47.0% ± 1.8, P < .001). In contrast, LV function deteriorated further in control animals. Compared with control animals, VM202-treated animals revealed peninsulas and/or islands of viable myocardium in infarcted and periinfarcted regions and greater number of capillaries (218 per square millimeter ± 19 vs 119 per square millimeter ± 17, P < .05) and arterioles (21 per square millimeter ± 4 vs 3 per square millimeter ± 1, P < .001). Conclusion: Intramyocardial transfer of VM202 improved myocardial

  15. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.

    PubMed

    Wang, Kai; Zhou, Xiaorong; Huang, Yanming; Khalil, Mazen; Wiktor, Dominik; van Giezen, J J J; Penn, Marc S

    2010-09-01

    Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. PMID:20694285

  16. Double-nuclide study of the myocardium using 201Tl and 123I-labeled fatty acids in non-ischemic myocardial diseases.

    PubMed

    Knapp, W H; Vyska, K; Machulla, H J; Notohamiprodjo, G; Schmidt, U; Knust, E J; Gleichmann, U

    1988-06-01

    Metabolic impairment and perfusion abnormalities are known to occur in hypertensive heart disease (HHD) and in cardiomyopathies. Free fatty acid (FFA) extraction is severely inhibited in a number of pathobiochemical reactions. This parameter was assessed using the radiolabeled FFA analogue 123I-(p-iodo-phenyl-)-pentadecanoic acid (IPPA) and 201Tl as perfusion marker, both of them injected at maximal physical workload. The regional extraction fraction of IPPA (IPPA-EF) was estimated by relating the regional IPPA and 201Tl uptake to each other. In HHD (normal coronary arteries) with posterior wall thickness less than or equal to 12 mm IPPA-EF was 77 +/- 18% (SD) in septum and 92 +/- 17% in the posterolateral wall (N = 13), with thickness of greater than 12 mm 60 +/- 23% in septum and 61 +/- 20% in the posterolateral wall (N = 8) when compared with IPPA-EF in normal subjects (= 100%, N = 9). In hypertrophic cardiomyopathy (HCM) IPPA-EF averaged 51 +/- 20% in septum and 87 +/- 10% in the posterolateral wall (N = 11). In these patient groups no systematic regional changes in 201TI uptake were observed. In dilated cardiomyopathy (DCM) both IPPA-EF and 201Tl uptake showed distinct regional variations and a great interindividual variability with a mean IPPA-EF reduction of 12% (N = 9). Thus, IPPA uptake in primarily non-ischemic myocardial disease may already be compromised when 201Tl uptake is unchanged. The double-nuclide method for IPPA-EF determination allows to eliminate the influence of flow in FFA imaging and enhances the potential of scintigraphy in the differential diagnosis of HHD versus coronary artery disease. PMID:3405780

  17. Improved myocardium transducer

    NASA Technical Reports Server (NTRS)

    Culler, V. H.; Feldstein, C.; Lewis, G. W.

    1979-01-01

    Method of implanting myocardium transducer uses special indented pins that are caught and securely held by epicardial fibers. Pins are small enough to cause minimum of trauma to myocardium during implantation or removal.

  18. [Phenomenon of heart ischemic postconditioning].

    PubMed

    Maslov, L N; Mrochek, A G; Hanus, L; Pei, J -M; Zhang, Y; Wang, H; Naryzhnaia, N V

    2012-08-01

    Authors of review analyzed papers on problem of heart ischemic postconditioning. In the review, it was demonstrated that postconditioning decreased an infarct size, prevented cardiomyocytes apoptosis, improved cardiac contractility in reperfusion period, augmented cardiac tolerance to arrhythmogenic impact ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress in myocardium. PMID:23155619

  19. Angiogenesis in the Infarcted Myocardium

    PubMed Central

    Cochain, Clement; Channon, Keith M.

    2013-01-01

    Abstract Significance: Proangiogenic therapy appeared a promising strategy for the treatment of patients with acute myocardial infarction (MI), as de novo formation of microvessels, has the potential to salvage ischemic myocardium at early stages after MI, and is also essential to prevent the transition to heart failure through the control of cardiomyocyte hypertrophy and contractility. Recent Advances: Exciting preclinical studies evaluating proangiogenic therapies for MI have prompted the initiation of numerous clinical trials based on protein or gene transfer delivery of growth factors and administration of stem/progenitor cells, mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed results in patients with acute MI. Critical Issues: Even though methodological caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs. gene transfer) and stem/progenitor cells or isolation/culture procedure for regenerative cells might partially explain the failure of such trials, it appears that delivery of a single growth factor or cell type does not support angiogenesis sufficiently to promote cardiac repair. Future Directions: Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI. Antioxid. Redox Signal. 18, 1100–1113. PMID:22870932

  20. Concentrated Ambient Particles Alter Myocardial Blood Flow during Acute Ischemia in Conscious Canines

    PubMed Central

    Bartoli, Carlo R.; Wellenius, Gregory A.; Coull, Brent A.; Akiyama, Ichiro; Diaz, Edgar A.; Lawrence, Joy; Okabe, Kazunori; Verrier, Richard L.; Godleski, John J.

    2009-01-01

    Background Experimental and observational studies have demonstrated that short-term exposure to ambient particulate matter (PM) exacerbates myocardial ischemia. Objectives We conducted this study to investigate the effects of concentrated ambient particles (CAPs) on myocardial blood flow during myocardial ischemia in chronically instrumented conscious canines. Methods Eleven canines were instrumented with a balloon occluder around the left anterior descending coronary artery and catheters for determination of myocardial blood flow using fluorescent microspheres. Telemetric electrocardiographic and blood pressure monitoring was available for four of these animals. After recovery, we exposed animals by inhalation to 5 hr of either filtered air or CAPs (mean concentration ± SD, 349.0 ± 282.6 μg/m3) in a crossover protocol. We determined myocardial blood flow during a 5-min coronary artery occlusion immediately after each exposure. Data were analyzed using mixed models for repeated measures. The primary analysis was based on four canines that completed the protocol. Results CAPs exposure decreased total myocardial blood flow during coronary artery occlusion by 0.12 mL/min/g (p < 0.001) and was accompanied by a 13% (p < 0.001) increase in coronary vascular resistance. Rate–pressure product, an index of myocardial oxygen demand, did not differ by exposure (p = 0.90). CAPs effects on myocardial blood flow were significantly more pronounced in myocardium within or near the ischemic zone versus more remote myocardium (p interaction < 0.001). Conclusions These results suggest that PM exacerbates myocardial ischemia by increased coronary vascular resistance and decreased myocardial perfusion. Further studies are needed to elucidate the mechanism of these effects. PMID:19337504

  1. Longitudinal rotating frame relaxation time measurements in infarcted mouse myocardium in vivo.

    PubMed

    Musthafa, Haja-Sherief N; Dragneva, Galina; Lottonen, Line; Merentie, Mari; Petrov, Lyubomir; Heikura, Tommi; Ylä-Herttuala, Elias; Ylä-Herttuala, Seppo; Gröhn, Olli; Liimatainen, Timo

    2013-05-01

    Longitudinal relaxation time in the rotating frame (T1ρ) was measured using continuous wave irradiation in normal and infarcted mouse myocardium in vivo. Significant increase in T1ρ was found after 7 days of infarction when compared with reference myocardium or in myocardium before infarction. Cine MRI and histology were performed to verify the severity of infarction. The time course of T1ρ in the infarct fits better with granulation and scar tissue formation than necrosis and edema. The results of the study show that T1ρ could potentially be a noninvasive quantitative marker for tissue remodeling after ischemic damage. PMID:22736543

  2. Canine Distemper

    MedlinePlus

    Although this brochure provides basic information about canine distemper, your veterinarian is always your best source of health information. Consult your veterinarian for more information about canine distemper and its prevention. ...

  3. Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin.

    PubMed

    Kamijo, T; Kamei, K; Sugo, I; Kamiyama, T; Sudo, H; Ohba, Y

    1999-01-01

    The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an

  4. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  5. Ischemic tissue injury.

    PubMed Central

    Jennings, R. B.; Ganote, C. E.; Reimer, K. A.

    1975-01-01

    The subendocardial to subepicardial gradient in the severity of ischemia following acute coronary occlusion is described. The effects of mild, moderate, and severe ischemia on cell structure and function are compared in summary form, and special attention is given to the effects of severe ischemia on myocardial cells. The characteristics of reversible and irreversible ischemic injury are defined in biologic terms. The failure of cell volume regulation in cells which have entered an irreversible state of ischemic injury is demonstrated by the use of free-hand slices in vitro. Irreversibility is associated with structural defects in the plasma membrane and is reflected in an increased slice inulin-diffusible space, increased slice H2O and Na+ content, and failure of the tissue to maintain the high K+ and Mg2+ levels characteristic of normal left ventricular myocardium. Defective cell membrane function is an early feature of irreversible ischemic injury and may be a primary event in the genesis of the irreversible state. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1180331

  6. Shock-induced arrhythmogenesis in the myocardium

    NASA Astrophysics Data System (ADS)

    Trayanova, Natalia; Eason, James

    2002-09-01

    The focus of this article is the investigation of the electrical behavior of the normal myocardium following the delivery of high-strength defibrillation shocks. To achieve its goal, the study employs a complex three-dimensional defibrillation model of a slice of the canine heart characterized with realistic geometry and fiber architecture. Defibrillation shocks of various strengths and electrode configurations are delivered to the model preparation in which a sustained ventricular tachycardia is induced. Instead of analyzing the post-shock electrical events as progressions of transmembrane potential maps, the study examines the evolution of the postshock phase singularities (PSs) which represent the organizing centers of reentry. The simulation results demonstrate that the shock induces numerous PSs the majority of which vanish before the reentrant wavefronts associated with them complete half of a single rotation. Failed shocks are characterized with one or more PSs that survive the initial period of PS annihilation to establish a new postshock arrhythmia. The increase in shock strength results in an overall decrease of the number of PSs that survive over 200 ms after the end of the shock; however, the exact behavior of the PSs is strongly dependent on the shock electrode configuration.

  7. A "second window of protection" occurs 24 h after ischemic preconditioning in the rat heart.

    PubMed

    Yamashita, N; Hoshida, S; Taniguchi, N; Kuzuya, T; Hori, M

    1998-06-01

    We and others found that cardioprotection is acquired not only soon after, but also 24 h after ischemic preconditioning in canine and rabbit myocardial infarction models (second window of protection). However, a second window phenomenon against myocardial infarction was dependent on species limitations and has not been observed in porcine hearts. In this study, we examined whether the "second window of protection" against myocardial infarction is observed in the rat heart. In the ischemic preconditioning (IP) group, the left main coronary artery (LCA) of rats was occluded four times for 3 min. each separated by reperfusion for 10 min. After 0, 3, and 24 h, the rats were subjected to a 20-min LCA occlusion followed by 48-h reperfusion. At 0 and 24 h after IP, infarct size and the incidence of ventricular fibrillation (VF) during ischemia were significantly reduced compared with corresponding sham-operated groups without preconditioning. After 3 h of IP, there were no differences either in the incidence of VF during ischemia or in infarct size. Manganese superoxide dismutase (Mn-SOD) content in ischemic (LCA) region of myocardium significantly increased as compared with that of sham-operated rats 24 h after IP. Treatment with N-2-mercaptopropionyl glycine, an antioxidant and a hydroxyl radical scavenger, during IP abolished the early-phase (0 h after IP) and late-phase (24 h after IP) cardioprotection and the corresponding late increase in Mn-SOD content. These results indicate that a "second window of protection" against myocardial infarction also exists in rat hearts and the induction of an intrinsic scavenger, Mn-SOD, via free radical production during IP may be important in the second window of protection. PMID:9689592

  8. [Nuclear magnetic resonance in ischemic cardiopathy].

    PubMed

    Meave, Aloha

    2007-01-01

    Nuclear magnetic resonance is the "gold standard" technique to quantify the ventricular volume, the ejection fraction, and the myocardial mass. In patients suffering from ischemic cardiopathy, the ejection fraction is the most important prognostic parameter, even above from lessoned arteries index. An adequate diagnose between a non-viable and a viable myocardium is of great importance in the therapeutic approach for ischemic cardiopathy. By administrating a paramagnetic contrast media named gadolinium, fist pass and late-reinforcement techniques, are applied. With these, it is possible to evaluate the perfusion as well as necrotic areas. In order to identify sub-endocardium ischemia, drugs such as adenosine and dipiridamol, are employed as vasodilators. This technique allows the definition of reinforcement extension, being sub-endocardiac, which is an ailment which affects 50% of the myocardium depth, or even, transmural compromise. PMID:18938717

  9. Myocardial kinetics of fluorine-18 misonidazole: A marker of hypoxic myocardium

    SciTech Connect

    Shelton, M.E.; Dence, C.S.; Hwang, D.R.; Welch, M.J.; Bergmann, S.R.

    1989-03-01

    Fluoromisonidazole, a member of a class of compounds referred to as ''hypoxic sensitizers,'' accumulates in hypoxic, viable tumor cells. We hypothesized that it might therefore accumulate also in ischemic, but non-necrotic myocardium potentially salvageable by interventional therapy. To evaluate the myocardial kinetics of (18F)fluoromisonidazole (FM), 20 isolated perfused rabbit hearts were used to characterize the uptake and binding of tracer under control conditions (n = 6), or with ischemia (flow 10% of control, n = 5), hypoxia without low flow (control flow rates with hypoxic medium, n = 5), or with reperfusion (n = 4). Myocardial retention of tracer detected externally with gamma scintillation probes after 20 min of constant (18F)FM infusion followed by 20 min of washout with nonradioactive buffer was 41 +/- 7% and 46 +/- 8% of peak activity in hearts subjected to ischemia or hypoxia, respectively, and significantly higher than in hearts subjected to either control perfusion or to ischemia followed by reperfusion (18 +/- 6 and 16 +/- 5% of peak activity, respectively, p less than 0.01). The biologic half-time of retained tracer was 40 hr in all hearts indicating essentially irreversible binding. Based on these findings, we measured uptake of (18F)FM using positron emission tomography in five dogs subjected to acute coronary occlusion. Five to thirteen millicuries of tracer were injected within 3 hr of occlusion. Within 30 min after administration of tracer, 18F accumulation in ischemic myocardium was greater than that observed in normal myocardium. The results indicate that (18F)FM accumulates in ischemic myocardium in relation to diminished tissue oxygen content and not simply because of diminished flow. Thus, this class of compounds may be potentially useful to help identify hypoxic myocardium.

  10. Regional myocardial shape and dimensions of the working isolated canine left ventricle

    NASA Technical Reports Server (NTRS)

    Ritman, E. L.; Tsuiki, K.; Donald, D.; Wood, E. H.

    1975-01-01

    The extent to which the dynamic shape and dimensions of the isolated left ventricular myocardial wall differ throughout the myocardium and how these differences are characteristic of the anatomic location was demonstrated. The use of a biplane X-ray technique and a metabolically-supported isolated canine left ventricle preparation provided an angiographically ideal means of measuring mechanical dynamics of the myocardium while the intact left ventricular myocardial structure and electrical activation pattern retains most of the in situ ventricular characteristics.

  11. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  12. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  13. Canine Parvovirus

    MedlinePlus

    Finally, do not let your puppy or adult dog to come into contact with the fecal waste of other dogs while walking or playing outdoors. Prompt and proper ... advisable as a way to limit spread of canine parvovirus infection as well as other diseases that ...

  14. Detection and quantification of thermal injury to the myocardium using ultrasound

    NASA Astrophysics Data System (ADS)

    Friedl, Stephan E.; Weng, Yishin; Mathews, Eric D.; Abela, George S.

    1992-08-01

    Selective thermal coagulation of discrete portions of the myocardium is becoming an accepted method for the treatment of various supraventricular tachyarrhythmias. This paper investigates the use of conventional ultrasonography for the detection and measurement of thermally coagulated lesions in myocardial tissue. Lesions were created in necropsied canine myocardium using a side-emitting laser catheter delivering cw Nd:YAG laser energy. Following irradiation, the sites were scanned with a 20 Mhz ultrasound catheter and the maximum depth of thermal damage was measured from the ultrasonographic imagery. The surface dimensions and transmural depth of thermal damage was then measured morphometrically with a video microscopy system. Depth measured by ultrasound was found to correlate well with depth by morphometry (r equals 0.78). Both depth measured by morphometry and by ultrasound were found to correlate well with the volume of thermal damage by morphometry (r equals 0.83 and r equals 0.77 respectively). Intraventricular ultrasonography may prove useful for in-vivo detection and measurement of thermally induced lesions in the myocardium. Additionally, it may also be applied for guidance and real-time monitoring of thermal coagulation of the myocardium during various arrhythmia ablation procedures.

  15. Canine leishmaniosis.

    PubMed

    Sapierzyński, R

    2008-01-01

    Canine visceral leishmaniosis (CVL) is an infectious disease of zoonotic potential, caused by protozoan parasite of the genus Leishmania. Common clinical manifestations of canine visceral leishmaniosis include decrease of appetite, progressive weight loss, exercise intolerance, peripheral lymph node and spleen enlargement, chronic renal and liver disease, muscle, atrophy, polyarthritis and others. Because the Polish literature in the field contains no information on leishmaniosis in animals the recognised case of this disease is presented. Homeless mongrel, intact female dog, 3 years of age was brought to a veterinary clinic because of apathy, and generalised dermatologic lesions to perform routine examination. Because therapeutic effect of primarily recognised scabies was unsatisfactory, the skin samples from ear margins, trunk and lesion of the area of the left gluteal region for histopatologic examination were taken. Due to suspicion of leishmaniosis, fine-needle aspiration biopsy of lymph nodes, skin lesions, ocular discharge and imprint samples from skin lesion were performed, and tissue collected were examined under optical microscopy for identification of Leishmania amastigotes. To confirm cytologic diagnosis, blood samples for serological tests (enzyme-linked immunoabsorbent assay-ELISA; indirect immunofluorescence assay test-IFAT) were taken. Based on physical examination, histopatology, cytopathology and serology, canine visceral leishmaniosis was finally diagnosed. PMID:18683546

  16. [Ischemic myocardial metabolism and antianginal drugs].

    PubMed

    Ichihara, K

    1986-12-01

    The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium. PMID:3549484

  17. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  18. Concomitant canine distemper, infectious canine hepatitis, canine parvoviral enteritis, canine infectious tracheobronchitis, and toxoplasmosis in a puppy.

    PubMed

    Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Fritzen, Juliana Torres Tomazi; Garcia, João Luis; Weissenböck, Herbert; da Silva, Ana Paula; Bodnar, Livia; Okano, Werner; Alfieri, Alice Fernandes

    2013-01-01

    The concomitant infections of Canine distemper virus (CDV), Canine adenovirus A types 1 (CAdV-1) and 2 (CAdV-2), Canine parvovirus type 2 (CPV-2), and Toxoplasma gondii are described in a 43-day-old mixed-breed puppy. Clinically, there were convulsions and blindness with spontaneous death; 14 siblings of this puppy, born to a 10-month-old dam, which was seropositive (titer: 1,024) for T. gondii, also died. Necropsy revealed unilateral corneal edema (blue eye), depletion of intestinal lymphoid tissue, non-collapsible lungs, congestion of meningeal vessels, and a pale area in the myocardium. Histopathology demonstrated necrotizing myocarditis associated with intralesional apicomplexan protozoa; necrotizing and chronic hepatitis associated with rare intranuclear inclusion bodies within hepatocytes; necrotizing bronchitis and bronchiolitis; interstitial pneumonia associated with eosinophilic intracytoplasmic inclusion bodies within epithelial cells; atrophy and fusion of intestinal villi with cryptal necrosis; and white matter demyelination of the cerebrum and cerebellum associated with intranuclear inclusion bodies within astrocytes. Polymerase chain reaction (PCR) amplified the partial fragments (bp) of the CDV N gene (290 bp), CPV-2c VP2 capsid protein gene (583 bp), and CAdV-1 (508 bp) and CAdV-2 (1,030 bp) E gene from urine and tissue samples. The PCR assays demonstrated that the apicomplexan protozoa observed within several organs contained DNA specific for T. gondii; genotyping revealed T. gondii type III. The findings support the characterization of concomitant infections of CDV, CAdV-1, CAdV-2, CPV-2, and T. gondii in this puppy. Further, seroreactivity to T. gondii of the dam in association with the systemic disease observed in the puppy described herein is suggestive of congenital toxoplasmosis. PMID:23293164

  19. Nanoparticles-Assisted Stem Cell Therapy for Ischemic Heart Disease

    PubMed Central

    Zhu, Kai; Li, Jun; Wang, Yulin; Lai, Hao; Wang, Chunsheng

    2016-01-01

    Stem cell therapy has attracted increasing attention as a promising treatment strategy for cardiac repair in ischemic heart disease. Nanoparticles (NPs), with their superior physical and chemical properties, have been widely utilized to assist stem cell therapy. With the help of NPs, stem cells can be genetically engineered for enhanced paracrine profile. To further understand the fate and behaviors of stem cells in ischemic myocardium, imaging NPs can label stem cells and be tracked in vivo under multiple modalities. Besides that, NPs can also be used to enhance stem cell retention in myocardium. These facts have raised efforts on the development of more intelligent and multifunctional NPs for cellular application. Herein, an overview of the applications of NPs-assisted stem cell therapy is given. Key issues and future prospects are also critically addressed. PMID:26839552

  20. Canine lymphoma

    SciTech Connect

    Weller, R.E.

    1986-10-01

    Canine lymphoma has served as the ''workhorse'' for the development of veterinary oncology and as an important animal model for human non-Hodgkins lymphomas. Significant advances have been achieved in understanding the biological behavior of the disease and in its treatment. Although it is unlikely that a cure for lymphoma will be achieved, owners should be encouraged to treat their pets, provided they understand that only prolonged remissions and survivals are likely to result. Cooperative studies, employing large numbers of dogs, are needed to optimize and refine the classification scheme to provide a system with diagnostic and prognostic correlates and derive maximum benefit from therapeutic regimens. Such studies need to be prospective in nature, with a solid statistical base incorporated into their design. Rather than being content with what we have accomplished to date in treatment of canine lymphoma, the opportunity exists for the veterinary profession to make further significant contributions to the understanding and treatment of lymphoma in the dog. 10 refs., 4 tabs.

  1. Stem Cell Therapy for Ischemic Heart Disease

    PubMed Central

    Jameel, Mohammad Nurulqadr

    2010-01-01

    Abstract Stem cell transplantation has emerged as a novel treatment option for ischemic heart disease. Different cell types have been utilized and the recent development of induced pluripotent stem cells has generated tremendous excitement in the regenerative field. Bone marrow-derived multipotent progenitor cell transplantation in preclinical large animal models of postinfarction left ventricular remodeling has demonstrated long-term functional and bioenergetic improvement. These beneficial effects are observed despite no significant engraftment of bone marrow cells in the myocardium and even lower differentiation of these cells into cardiomyocytes. It is thought to be related to the paracrine effect of these stem cells, which secrete factors that lead to long-term gene expression changes in the host myocardium, thereby promoting neovascularization, inhibiting apoptosis, and stimulating resident cardiac progenitor cells. Future studies are warranted to examine the changes in the recipient myocardium after stem cell transplantation and to investigate the signaling pathways involved in these effects. Antioxid. Redox Signal. 13, 1879–1897. PMID:20687781

  2. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  3. Ischemic preconditioning protects against ischemic brain injury.

    PubMed

    Ma, Xiao-Meng; Liu, Mei; Liu, Ying-Ying; Ma, Li-Li; Jiang, Ying; Chen, Xiao-Hong

    2016-05-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  4. Exercise preconditioning of the myocardium.

    PubMed

    Kavazis, Andreas N

    2009-01-01

    Diseases of the heart (e.g. myocardial ischaemia reperfusion injury) remain the major cause of death in the industrialized world. Therefore, developing a pragmatic countermeasure to reduce myocardial ischaemia reperfusion injury is vital. In this regard, a plethora of evidence indicates that regular exercise can protect the heart during an ischaemia reperfusion insult (i.e. cardioprotection). This review summarizes studies indicating that both short-term (i.e. 1-5 days) and long-term (i.e. weeks to months) endurance exercise provides cardioprotection. Data are presented showing that exercise duration and exercise intensity are both important factors in achieving a cardioprotective phenotype. Importantly, it appears that the exercise duration of a single exercise session should last for 60 minutes and should be performed at about 75% maximum oxygen consumption in order to achieve exercise-induced cardioprotection. Furthermore, data are presented showing that exercise-induced cardioprotection against myocardial stunning can persist for at least 9 days after the cessation of exercise training, but is lost 18 days after exercise. This review also summarizes the exercise-induced adaptations that occur to the myocardium. In particular, extrinsic changes observed in human and animal models include neural, hormonal, humoral, vascular and reduced body fat. Other anatomical and biochemical/molecular changes that have been studied as putative mechanisms in exercise-induced cardioprotection include alterations in anatomic coronary arteries, induction of myocardial heat shock proteins, increased myocardial cyclooxygenase-2 activity, elevated endoplasmic reticulum stress proteins, nitric oxide production, improved function of sarcolemmal and/or mitochondrial adenosine triphosphate (ATP)-sensitive potassium channels and increased myocardial antioxidant capacity. However, the most compelling evidence for exercise-induced cardioprotection is the fact that exercise training

  5. Canine hyperlipidaemia.

    PubMed

    Xenoulis, P G; Steiner, J M

    2015-10-01

    Hyperlipidaemia refers to an increased concentration of lipids in the blood. Hyperlipidaemia is common in dogs and has recently emerged as an important clinical condition that requires a systematic diagnostic approach and appropriate treatment. Hyperlipidaemia can be either primary or secondary to other diseases. Secondary hyperlipidaemia is the most common form in dogs, and it can be a result of endocrine disorders, pancreatitis, cholestasis, protein-losing nephropathy, obesity, as well as other conditions and the use of certain drugs. Primary hyperlipidaemia is less common in the general canine population but it can be very common within certain breeds. Hypertriglyceridaemia of Miniature Schnauzers is the most common form of primary hyperlipidaemia in dogs but other breeds are also affected. Possible complications of hyperlipidaemia in dogs include pancreatitis, liver disease, atherosclerosis, ocular disease and seizures. Management of primary hyperlipidaemia in dogs is achieved by administration of ultra low-fat diets with or without the administration of lipid lowering drugs such as omega-3 fatty acids, fibrates, niacin and statins. PMID:26456868

  6. The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart.

    PubMed

    Evans, Cameron W; Iyer, K Swaminathan; Hool, Livia C

    2016-04-01

    Treatment of acute cardiac ischemia remains an area in which there are opportunities for therapeutic improvement. Despite significant advances, many patients still progress to cardiac hypertrophy and heart failure. Timely reperfusion is critical in rescuing vulnerable ischemic tissue and is directly related to patient outcome, but reperfusion of the ischemic myocardium also contributes to damage. Overproduction of reactive oxygen species, initiation of an inflammatory response and deregulation of calcium homeostasis all contribute to injury, and difficulties in delivering a sufficient quantity of drug to the affected tissue in a controlled manner is a limitation of current therapies. Nanotechnology may offer significant improvements in this respect. Here, we review recent examples of how nanoparticles can be used to improve delivery to the ischemic myocardium, and suggest some approaches that may lead to improved therapies for acute cardiac ischemia. PMID:26980180

  7. Free radical metabolites in myocardium during ischemia and reperfusion.

    PubMed

    Ruuge, E K; Ledenev, A N; Lakomkin, V L; Konstantinov, A A; Ksenzenko MYu

    1991-10-01

    Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20-30 min of normothermic ischemia or 10-30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5-50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical "doublet" signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium approximately 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20-30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart. PMID:1656795

  8. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Jul 12,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  9. Myocardium wall thickness transducer and measuring method

    NASA Technical Reports Server (NTRS)

    Feldstein, C.; Lewis, G. W.; Silver, R. H.; Culler, V. H. (Inventor)

    1976-01-01

    A miniature transducer for measuring changes of thickness of the myocardium is described. The device is easily implantable without traumatizing the subject, without affecting the normal muscle behavior, and is removable and implantable at a different muscle location. Operating features of the device are described.

  10. Ischemia in collateral-dependent myocardium: effects of nifedipine and diltiazem in man.

    PubMed

    Pupita, G; Mazzara, D; Centanni, M; Rimatori, C; Ferretti, G F; Dessì-Fulgheri, P; Russo, P; Rappelli, A

    1993-07-01

    It has recently been shown that ischemia in collateral-dependent myocardium may develop at a very variable threshold in anginal patients; accordingly, the aim of this study was to assess whether nifedipine and diltiazem can increase blood flow to collateralized myocardium in man. Nine patients with complete coronary occlusion filled by collaterals, with no other coronary stenosis, normal left ventricular function, and reproducibly positive exercise tests were studied. They underwent exercise tests off therapy and after acute randomized administration of nifedipine (10 mg sublingually), diltiazem (120 mg orally), and nitroglycerin (0.5 mg sublingually), the latter a drug known to increase blood flow to collateralized myocardium. Following nifedipine, time to 1 mm ST segment depression increased significantly (from 430 +/- 176 to 576 +/- 205 seconds, p < 0.01), while heart rate and rate-pressure product remained unchanged (115 +/- 16 vs 121 +/- 17 beats/min and 199 +/- 29 vs 204 +/- 44 beats/min.mm Hg.10(2), respectively, p = NS for both). Similarly, diltiazem significantly increased time to ischemic threshold from baseline to 638 +/- 125 seconds (p < 0.01), but did not change heart rate and rate-pressure product at 1 mm ST segment depression. Submaximal rate-pressure products were significantly lowered by both nifedipine and diltiazem. Nitroglycerin not only significantly improved time to ischemic threshold (from baseline to 666 +/- 76 seconds, p < 0.01), but also increased heart rate (from baseline to 137 +/- 16 beats/min, p < 0.01) and rate-pressure product (from baseline to 242 +/- 48 beats/min.mm Hg.10(2), p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8322695

  11. Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction

    SciTech Connect

    Fujita, M.; Ohno, A.; Wada, O.; Miwa, K.; Nozawa, T.; Yamanishi, K.; Sasayama, S. )

    1991-08-01

    The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 {plus minus} 0.5 (SD), which was significantly higher than the 0.7 {plus minus} 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

  12. Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction.

    PubMed

    Lee, Min Su; Park, Hyun Soo; Lee, Byung Chul; Jung, Jae Ho; Yoo, Jung Sun; Kim, Sang Eun

    2016-01-01

    Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvβ3. Here, we describe the capability of an αvβ3 integrin-targeting SPECT agent, (99m)Tc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with (201)Tl SPECT and (18)F-FDG PET, then, proved that such prominent uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was non-inferior to that of (18)F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvβ3 integrin. Together, these results establish that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization. PMID:27283041

  13. Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction

    PubMed Central

    Lee, Min Su; Park, Hyun Soo; Lee, Byung Chul; Jung, Jae Ho; Yoo, Jung Sun; Kim, Sang Eun

    2016-01-01

    Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvβ3. Here, we describe the capability of an αvβ3 integrin-targeting SPECT agent, 99mTc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of 99mTc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with 201Tl SPECT and 18F-FDG PET, then, proved that such prominent uptake of 99mTc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of 99mTc-IDA-D-[c(RGDfK)]2 was non-inferior to that of 18F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of 99mTc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvβ3 integrin. Together, these results establish that 99mTc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization. PMID:27283041

  14. Localization of Impacted Canines

    PubMed Central

    Mehrotra, Praveen; Bhagchandani, Jitendra; Singh, Ashish; Garg, Aarti; Kumar, Snehi; Sharma, Ashish; Yadav, Harsh

    2015-01-01

    Impaction of maxillary canines is a frequently encountered clinical problem. The impaction of canine can be prevented in some situationsif the canine displacement is diagnosed in the early mixed dentition period and this would be extremely useful for the clinician. Hence,it is very important to focus on the means of early diagnosis and interception of this clinical situation. In the present article, the differentmodalities used to diagnose the impacted canine are reviewed with an insight into current 3-D modalities. PMID:25738100

  15. Prolonged contraction duration in aged myocardium.

    PubMed

    Lakatta, E G; Gerstenblith, G; Angell, C S; Shock, N W; Weisfeldt, M L

    1975-01-01

    Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content. PMID:1109181

  16. Remote ischemic conditioning: a clinical trial's update.

    PubMed

    Candilio, Luciano; Hausenloy, Derek J; Yellon, Derek M

    2011-01-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome. This process can, however, induce further myocardial damage, namely acute myocardial ischemia-reperfusion injury (IRI) and worsen clinical outcome. Therefore, novel therapeutic strategies are required to protect the myocardium against IRI in patients with CAD. In this regard, the endogenous cardioprotective phenomenon of "ischemic conditioning," in which the heart is put into a protected state by subjecting it to one or more brief nonlethal episodes of ischemia and reperfusion, has the potential to attenuate myocardial injury during acute IRI. Intriguingly, the heart can be protected in this manner by applying the "ischemic conditioning" stimulus to an organ or tissue remote from the heart (termed remote ischemic conditioning or RIC). Furthermore, the discovery that RIC can be noninvasively applied using a blood pressure cuff on the upper arm to induce brief episodes of nonlethal ischemia and reperfusion in the forearm has greatly facilitated the translation of RIC into the clinical arena. Several recently published proof-of-concept clinical studies have reported encouraging results with RIC, and large multicenter randomized clinical trials are now underway to investigate whether this simple noninvasive and virtually cost-free intervention has the potential to improve clinical outcomes in patients with CAD. In this review article, we provide an update of recently published and ongoing clinical trials in the field of RIC. PMID:21821533

  17. Backscatter and attenuation characterization of ventricular myocardium

    NASA Astrophysics Data System (ADS)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  18. Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis.

    PubMed Central

    Geer, J. C.; Crago, C. A.; Little, W. C.; Gardner, L. L.; Bishop, S. P.

    1980-01-01

    Morphologic changes in the subendocardial myocardium that appeared to be caused by severe, chronic subendocardial ischemia were studied in patients with fatal ischemic heart disease admitted to the Specialized Center of Research for Ischemic Heart Disease at the University of Alabama in Birmingham in the period 1970--1977. Thirteen patients were selected for this report on the basis that they had the lesions in the subendocardial myocardium we believe to have been caused by subendocardial ischemia and had no evidence of acute or remote myocardial infarction or other conditions that may have contributed to their terminal illness or death. Clinical findings were unstable angina, congestive heart failure, usually no increase in plasma enzymes indicative of myocardial damage, and electrocardiographic changes consistent with subendocardial ischemia. All 13 patients had 75% or greater stenosis of the three major coronary arteries; none had acute thrombotic or embolic coronary artery occlusion. The left ventricle in all cases was hypertrophied. The subendocardial myocardium showed circumferential pallor, hyperemia, or focal fibrosis without perceptible loss of volume in papillary muscles or trabeculae carneae. Microscopically, acute lesions showed one to two layers of preserved myofibers adjacent to the endocardium, vacuolar change in the deeper fibers, and focal areas of coagulation necrosis of variable size in the myocardium external to the fibers with vacuolar change. Coagulation necrosis was extensive in some cases and usually was not associated with infiltration of neutrophils. The repair reaction involved removal of necrotic sarcoplasm by mononuclear phagocytes, resulting in a reticular-appearing tissue without evidence of stromal collapse. Granulation tissue was not seen. Collagen fibers appeared to be deposited within the area of previous sarcolemmal sheaths. The distribution and morphology of subendocardial myocardial lesions associated with severe coronary

  19. [Characterization of the asynergic myocardium in acute coronary syndrome using simultaneous dual radionuclide emission computed tomography].

    PubMed

    Sone, T; Tsuboi, H; Sassa, H; Okumura, Y

    1990-01-01

    The purpose of the present study was to evaluate the tissue characterization of the ischemic myocardium by dual single photon emission computed tomography (SPECT) with thallium-201 (Tl-201) and technetium-99m pyrophosphate (Tc-99m PYP) using the simultaneous collection method. The subjects consisted of 84 patients with acute coronary syndrome followed by protracted left ventricular asynergy. For precise interpretation of clinical scintigraphy, we used phantom experiments and the results were as follows: 1. The residual myocardium in the infarcted area could be evaluated to some extent from the severity of the defect on Tl-201 SPECT with optimal and unified image processing standardized by maximal pixel counts in the myocardium. 2. The influence of cross talk between two radionuclides on each tomographic image was negligible under usual clinical conditions. 3. In a subendocardial infarction model where the Tc-99m layer was located within 50% inside the phantom wall and the other space was filled with 201TlCl solution, the Tc-99m layer was clearly visualized inwardly as compared with the Tl-201 layer on dual SPECT with optimal image processing. 4. Transmural infarction could be visualized as a total defect on Tl-201 SPECT only when its diameter was greater than 2 to 2.5 cm. Taking these results into account, we evaluated clinical cases. According to the peak CK value and Tl-201 SPECT in the chronic phase, the subjects were categorized as transmural infarction (TMI), nontransmural infarction (NTMI) and unstable angina pectoris (UAP), and the scintigraphic characteristics of each group were compared. Short-axis tomographic features of all lesions were classified in nine types from 1A to IIIC by the combination of Tl-201 uptake grades (total defect: I, reduced uptake: II, normal: III) and the condition of Tc-99m PYP accumulation (negative: A, transmural: B, subendocardial: C). The relationship between recovery from asynergy and the dual scintigraphic findings was also

  20. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

    PubMed

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features. PMID:26199786

  1. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium.

    PubMed

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S

    2016-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Finally, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  2. Noncompaction of the Ventricular Myocardium and Polycystic Kidney Disease: A Case Report.

    PubMed

    Fukino, Keiko; Ishiwata, Junpei; Shinohara, Hiroki; Oshima, Tsukasa; Kozaki, Tsunashi; Ikutomi, Masayasu; Amaki, Toshihiro; Nakamura, Fumitaka

    2016-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions. PMID:26873255

  3. Clinical study of the stunned myocardium.

    PubMed

    Sone, T; Tsuboi, H; Sassa, H

    1991-09-01

    Clinical features of 37 cases of stunned myocardium were studied. Mean duration of asynergy was 22.6 +/- 15.7 days. In all 11 cases of unstable angina without any significant serum creatine kinase leakage, the duration of asynergy was within 14 days. Related coronary lesions were reperfused (spontaneously or by interventional therapy) to TIMI grade II or higher. Transient Q waves were observed in 39% of all cases. Negative T waves tended to be prolonged, and persisted after disappearance of asynergy in 74% of all cases. 201Tl uptake in the stunned area varied widely between individual cases (ranging from "absent" to "normal"), although it became normal in all cases in the chronic stage. Mal-distribution of 99mTc-pyrophosphate (PYP) to the endocardial side of the stunned area was observed in 33%. In 186 cases of acute coronary syndrome, we studied whether or not reversibility of ischemia-disturbed myocardium could be predicted by simultaneous dual isotope SPECT, and found that 201Tl-uptake in the chronic stage significantly improved in the region showing absence of 99mTc-PYP accumulation or maldistribution of 99mTc-PYP to the endocardial side, while reversibility of the region showing transmural 99mTc-PYP accumulation and a dought pattern was poor. Ischemia-associated myocardial damage recovered to various degrees, and dual isotope SPECT was useful in evaluating the reversibility of such damage already at the acute stage. PMID:1834873

  4. Clinical Implications of Preserving Subvalvular Apparatus During Mitral Valve Replacement for Acute Ischemic Papillary Muscle Rupture.

    PubMed

    de Cannière, Didier; Vandenbossche, Jean-Luc; Nouar, Elias; Faict, Sebastian; Falchetti, Alessandro; Unger, Philippe

    2016-07-01

    We report the case of a patient who presented with sequential rupture of two papillary muscle bellies after emergent mitral valve replacement with subvalvular apparatus preservation for acute severe mitral regurgitation and cardiogenic shock during acute myocardial infarction. We discuss the possibility that the remaining chordae may have meanwhile contributed to muscle avulsion by exerting traction on ischemic myocardium and prevented embolization of the secondarily detached papillary muscle heads. PMID:27343501

  5. Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart.

    PubMed

    Ii, Masaaki; Horii, Miki; Yokoyama, Ayumi; Shoji, Taro; Mifune, Yutaka; Kawamoto, Atsuhiko; Asahi, Michio; Asahara, Takayuki

    2011-04-01

    Human multipotent adipose-derived stem cells (hMADSCs) have recently been isolated featuring extensive expansion capacity ex vivo. We tested the hypothesis that hMADSC transplantation might contribute to cardiac functional recovery by its direct or indirect effect on myocardial infarction (MI). Nude rats were either transplanted with hMADSCs or PBS (control) in ischemic myocardium immediately following MI. Echocardiographical assessment of cardiac function after MI with hMADSCs showed significant improvement of each parameter compared to that with PBS. Histological analysis also showed significantly reduced infarct size and increased capillary density in peri-infarct myocardium by hMADSC treatment. However, remarkable transdifferentiation of hMADSCs into cardiac or vascular lineage cells was not observed. Despite the less transdifferentiation capacity, hMADSCs produced robust multiple pro-angiogenic growth factors and chemokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1α (SDF-1α). Specifically, hMADSC-derived SDF-1α had a crucial role for cooperative angiogenesis, with the paracrine effect of hMADSCs and Tie2-positive bone marrow (BM) progenitor recruitment in ischemic myocardium. hMADSCs exhibit a therapeutic effect on cardiac preservation following MI, with the production of VEGF, bFGF, and SDF-1α showing paracrine effects and endogenous BM stem/progenitor recruitment to ischemic myocardium rather than its direct contribution to tissue regeneration. PMID:21135814

  6. Cardioprotection Acquired Through Exercise: The Role of Ischemic Preconditioning

    PubMed Central

    Marongiu, Elisabetta; Crisafulli, Antonio

    2014-01-01

    A great bulk of evidence supports the concept that regular exercise training can reduce the incidence of coronary events and increase survival chances after myocardial infarction. These exercise-induced beneficial effects on the myocardium are reached by means of the reduction of several risk factors relating to cardiovascular disease, such as high cholesterol, hypertension, obesity etc. Furthermore, it has been demonstrated that exercise can reproduce the “ischemic preconditioning” (IP), which refers to the capacity of short periods of ischemia to render the myocardium more resistant to subsequent ischemic insult and to limit infarct size during prolonged ischemia. However, IP is a complex phenomenon which, along with infarct size reduction, can also provide protection against arrhythmia and myocardial stunning due to ischemia-reperfusion. Several clues demonstrate that preconditioning may be directly induced by exercise, thus inducing a protective phenotype at the heart level without the necessity of causing ischemia. Exercise appears to act as a physiological stress that induces beneficial myocardial adaptive responses at cellular level. The purpose of the present paper is to review the latest data on the role played by exercise in triggering myocardial preconditioning. PMID:24720421

  7. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

  8. Genetic Modification of Mesenchymal Stem Cells Overexpressing CCR1 Increases Cell Viability, Migration, Engraftment and Capillary Density in the Injured Myocardium

    PubMed Central

    Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

    2010-01-01

    Rationale Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly due to poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (e.g. CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. Objective To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Methods and Results Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs three days post-myocardial infarction (MI). CCR1-MSC injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium three days post-MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks post-MI. Conclusions Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium. PMID:20378860

  9. [Effect of a galvanic current on ischemic damage to the myocardium].

    PubMed

    Mrochek, A G; Adzerikho, I E; Konev, S V

    1996-01-01

    Galvanization of precardial region in rats with experimental infarction elicits considerable cardioprotective effect manifested in a decrease of the mass of necrotic tissue and in partial normalization of ion content both in the necrotic focus and outside it. PMID:8723662

  10. X-ray microanalysis of calcium in ischemic myocardium: a new method of rapid freezing.

    PubMed

    Sybers, H D; Myre, C D; Myre, M V

    1983-01-01

    X-ray microanalysis of biological material is best accomplished on unfixed frozen tissue sectioned on a cryoultramicrotome. The need for ultra-rapid freezing to minimize ice crystal artifact has been well documented but is difficult to achieve without the use of potentially hazardous Isopentane or Freon 22 in liquid nitrogen slush. In the present study we employ a slurry of powdered graphite in liquid nitrogen to obtain rapid freezing of cardiac tissue. The results obtained were as good as those which are achieved with Freon 22 in liquid nitrogen, and subsequent cryoultramicrotomy produced thin sections relatively free of ice crystal artifact. Microanalysis revealed a slight increase in mitochondrial calcium as compared with cytoplasmic calcium in normal myocytes. Mitochondrial calcium concentration rose significantly after 30 min of ischemia while only a slight rise in cytoplasmic calcium occurred. These findings suggest that the techniques employed are adequate for detecting ion shifts which occur during ischemia and may be useful for determining the effects of therapeutic agents at the organellar level. PMID:6635573

  11. Delayed uptake and washout of contrast in non-viable infarcted myocardium shown with dynamic computed tomography

    PubMed Central

    Laugesen, Sofie; Agger, Peter; Hønge, Jesper; Smerup, Morten; Udholm, Nichlas; Bøtker, Hans Erik; Bøttcher, Morten

    2014-01-01

    Background Assessment of ischemic but potentially viable myocardium plays an important role in the planning of coronary revascularization. Until now SPECT, PET, and MRI have been used to identify viable myocardium. Computed tomography (CT) is increasingly used to diagnose coronary atherosclerosis. Objective To evaluate the feasibility of CT enhancement as a viability marker by investigating myocardial contrast distribution over time in pigs with experimentally induced antero-septal myocardial infarctions. Methods Twelve pigs were subjected to 60 min of balloon occlusion of the left anterior descending artery, followed by removal of the balloon and reperfusion. Four pigs died due to refractory ventricular fibrillation. After 6 weeks, dynamic cardiac CT was performed assessing both wall motion and contrast attenuation. Measurements of attenuation values in Hounsfield units (HU) in the infarct zone and the normal lateral wall were performed at 20 s, and 1, 3, 5, 8 and 12 min after contrast injection. Results We found highly significant differences in attenuation values between the two zones at all-time points except t =1 min (ANOVA P=0.85). The normal myocardium showed higher uptake- and washout-rates of contrast than the infarct zone (84±15 vs. 58±8 at 20 s, P=0.0001 and 27±12 vs. 81±13 at 12 min, P=0.0001). Specifically, the ratio between early (20 s) and late (12 min) uptake is a valid marker of viable myocardium. In all animals this ration was above one in the normal zone and below one in the infarct zone. Conclusions Delayed infarct related uptake and washout of contrast shows promise for future clinical application of CT in a combined assessment of coronary atherosclerosis and myocardial viability. PMID:25414821

  12. OCT imaging of myocardium extending to pulmonary vein

    NASA Astrophysics Data System (ADS)

    Li, Zhifang; Dickfeld, Timm; Tang, Qinggong; Wang, Bohan; Chen, Yu

    2016-02-01

    In this study, we propose to use optical coherence tomography to enable a direct visualization of myocardium extending into the pulmonary vein (PV). The results showed that there are obvious differences in the morphology of myocardium and fibrous tissue in the transition region of myocardial sleeve, which is in agreement with the histological analysis. In addition, the myocardial area in transition point has three layers in the depth of 1 mm, and the depth-resolved myocardial fiber show different orientation in the different layers. This characteristic was applied for segmentation of the structures of myocardium extending into PV.

  13. Creatine kinase overexpression improves ATP kinetics and contractile function in postischemic myocardium

    PubMed Central

    Akki, Ashwin; Su, Jason; Yano, Toshiyuki; Gupta, Ashish; Wang, Yibin; Leppo, Michelle K.; Chacko, Vadappuram P.; Steenbergen, Charles

    2012-01-01

    Reduced myofibrillar ATP availability during prolonged myocardial ischemia may limit post-ischemic mechanical function. Because creatine kinase (CK) is the prime energy reserve reaction of the heart and because it has been difficult to augment ATP synthesis during and after ischemia, we used mice that overexpress the myofibrillar isoform of creatine kinase (CKM) in cardiac-specific, conditional fashion to test the hypothesis that CKM overexpression increases ATP delivery in ischemic-reperfused hearts and improves functional recovery. Isolated, retrograde-perfused hearts from control and CKM mice were subjected to 25 min of global, no-flow ischemia and 40 min of reperfusion while cardiac function [rate pressure product (RPP)] was monitored. A combination of 31P-nuclear magnetic resonance experiments at 11.7T and biochemical assays was used to measure the myocardial rate of ATP synthesis via CK (CK flux) and intracellular pH (pHi). Baseline CK flux was severalfold higher in CKM hearts (8.1 ± 1.0 vs. 32.9 ± 3.8, mM/s, control vs. CKM; P < 0.001) with no differences in phosphocreatine concentration [PCr] and RPP. End-ischemic pHi was higher in CKM hearts than in control hearts (6.04 ± 0.12 vs. 6.37 ± 0.04, control vs. CKM; P < 0.05) with no differences in [PCr] and [ATP] between the two groups. Post-ischemic PCr (66.2 ± 1.3 vs. 99.1 ± 8.0, %preischemic levels; P < 0.01), CK flux (3.2 ± 0.4 vs. 14.0 ± 1.2 mM/s; P < 0.001) and functional recovery (13.7 ± 3.4 vs. 64.9 ± 13.2%preischemic RPP; P < 0.01) were significantly higher and lactate dehydrogenase release was lower in CKM than in control hearts. Thus augmenting cardiac CKM expression attenuates ischemic acidosis, reduces injury, and improves not only high-energy phosphate content and the rate of CK ATP synthesis in postischemic myocardium but also recovery of contractile function. PMID:22886411

  14. Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs

    PubMed Central

    Olivecrona, Göran K; Härdig, Bjarne Madsen; Roijer, Anders; Block, Mattias; Grins, Edgars; Persson, Hans W; Johansson, Leif; Olsson, Bertil

    2005-01-01

    Background The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium. Methods In an open chest porcine model (n = 17), myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA) was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria. Results Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 ± 2.0 vs. 4.3 ± 1.5 (mean ± standard deviation), (p = 0.004). In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 ± 1.7 vs. 6.2 ± 2.0 (p = 0.027). Conclusion Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified. PMID:15831106

  15. Model dependent behaviour of pressure hypertrophied myocardium.

    PubMed

    Cooper, G; Tomanek, R J

    1987-05-01

    Two animal models with contrasting responses to pressure overloading were used to determine whether cardiac dysfunction is a general property of pressure hypertrophied myocardium or a specific property of a particular model. Chronic progressive cardiac pressure overload was compared in (a) the left ventricle of the adult and aged spontaneously hypertensive rat, in which pressure overloading begins in the pup, and (b) the right ventricle of the adult cat, in which pressure overloading was initiated surgically in the kitten. Nine hypertensive and nine control rats were studied at 1 year of age, when hypertension is stable in this model; five hypertensive and five control rats were then studied at 2 years of age, when both groups of rats are beginning to show appreciable senile mortality. Systolic blood pressure was similarly increased in both hypertensive groups; compared with the normotensive control groups, the ratio of left ventricular to body weight was 36% and 76% higher in the 1 and 2 year old hypertensive groups respectively. During isotonic contractions of left ventricular papillary muscles the extent and velocity of shortening in muscles from the control and hypertensive rats in each group were the same, but shortening and relaxation times were prolonged in muscles from the hypertensive rats in both age groups. During isometric contractions developed tension and the rate of tension rise were the same throughout, but the time integral of active tension was increased in muscles from the hypertensive rats in both age groups. The ratio of oxygen consumption to either external work or developed tension was decreased in muscles from the hypertensive rats. In contrast to these data, previous data from the hypertrophied cat model showed reductions in both the velocity and the extent of isotonic shortening as well as in the rate and amount of isometric tension development, and prolongation of contraction was not observed. A similar but smaller decrease in the oxygen

  16. Vaccines for Canine Leishmaniasis

    PubMed Central

    Foroughi-Parvar, Faeze; Hatam, Gholamreza

    2014-01-01

    Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL). The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL) is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now. PMID:25628897

  17. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Hepatitis and Canine Adenovirus... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  18. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  19. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  20. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  1. Leukocytes Link Local and Systemic Inflammation in Ischemic Cardiovascular Disease: An Expanded "Cardiovascular Continuum".

    PubMed

    Libby, Peter; Nahrendorf, Matthias; Swirski, Filip K

    2016-03-01

    Physicians have traditionally viewed ischemic heart disease in a cardiocentric manner: plaques grow in arteries until they block blood flow, causing acute coronary and other ischemic syndromes. Recent research provides new insight into the integrative biology of inflammation as it contributes to ischemic cardiovascular disease. These results have revealed hitherto unsuspected inflammatory signaling networks at work in these disorders that link the brain, autonomic nervous system, bone marrow, and spleen to the atherosclerotic plaque and to the infarcting myocardium. A burgeoning clinical published data indicates that such inflammatory networks-far from a mere laboratory curiosity-operate in our patients and can influence aspects of ischemic cardiovascular disease that determine decisively clinical outcomes. These new findings enlarge the circle of the traditional "cardiovascular continuum" beyond the heart and vessels to include the nervous system, the spleen, and the bone marrow. PMID:26940931

  2. Computational Modeling of Healthy Myocardium in Diastole.

    PubMed

    Nikou, Amir; Dorsey, Shauna M; McGarvey, Jeremy R; Gorman, Joseph H; Burdick, Jason A; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F

    2016-04-01

    In order to better understand the mechanics of the heart and its disorders, engineers increasingly make use of the finite element method (FEM) to investigate healthy and diseased cardiac tissue. However, FEM is only as good as the underlying constitutive model, which remains a major challenge to the biomechanics community. In this study, a recently developed structurally based constitutive model was implemented to model healthy left ventricular myocardium during passive diastolic filling. This model takes into account the orthotropic response of the heart under loading. In-vivo strains were measured from magnetic resonance images (MRI) of porcine hearts, along with synchronous catheterization pressure data, and used for parameter identification of the passive constitutive model. Optimization was performed by minimizing the difference between MRI measured and FE predicted strains and cavity volumes. A similar approach was followed for the parameter identification of a widely used phenomenological constitutive law, which is based on a transversely isotropic material response. Results indicate that the parameter identification with the structurally based constitutive law is more sensitive to the assigned fiber architecture and the fit between the measured and predicted strains is improved with more realistic sheet angles. In addition, the structurally based model is capable of generating a more physiological end-diastolic pressure-volume relationship in the ventricle. PMID:26215308

  3. Impaired oxidative phosphorylation in overtrained rat myocardium

    PubMed Central

    Kadaja, Lumme; Eimre, Margus; Paju, Kalju; Roosimaa, Mart; Põdramägi, Taavi; Kaasik, Priit; Pehme, Ando; Orlova, Ehte; Mudist, Margareeta; Peet, Nadezhda; Piirsoo, Andres; Seene, Teet; Gellerich, Frank N; Seppet, Enn K

    2010-01-01

    The present study was undertaken to characterize and review the changes in energy metabolism in rat myocardium in response to chronic exhaustive exercise. It was shown that a treadmill exercise program applied for six weeks led the rats into a state characterized by decreased performance, loss of body weight and enhanced muscle catabolism, indicating development of overtraining syndrome. Electron microscopy revealed disintegration of the cardiomyocyte structure, cellular swelling and appearance of peroxisomes. Respirometric assessment of mitochondria in saponin-permeabilized cells in situ revealed a decreased rate of oxidative phosphorylation (OXPHOS) due to diminished control over it by ADP and impaired functional coupling of adenylate kinase to OXPHOS. In parallel, reduced tissue content of cytochrome c was observed, which could limit the maximal rate of OXPHOS. The results are discussed with respect to relationships between the volume of work and corresponding energy metabolism. It is concluded that overtraining syndrome is not restricted to skeletal muscle but can affect cardiac muscle as well. PMID:21264069

  4. The venous drainage of the human myocardium.

    PubMed

    von Lüdinghausen, M

    2003-01-01

    New cardiological techniques such as coronary sinus catheterization and selective catheterization of the cardiac veins permit the opening of new experimental and clinical fields, for instance in venous angiography and the reverse nourishment of myocardium which is endangered by ischemia,and also in the electrophysiological study of the components of the conduction system. New approaches in heart surgery, such as the removal of accessory pathways of the conduction system (as in WPW syndrome), necessitate the realization of the topographical relationships of the vessels in the various sections of the coronary sulci in a different way. The objective of this work is, therefore, to present comprehensive and almost new macro- and microanatomical data about the venous drainage of the myocardium via the coronary sinus and its related and unrelated (non-coronary) cardiac veins. Examination of meticulously dissected heart specimens (of individuals who had achieved old or extreme old age at the time of their death in Germany: n=250) as well as corrosion casts of adult cardiac vessels (of individuals of all ages, n=25) formed the basis for the exact description and documentation of the occurrence, frequency, origin, and courses of both the normal and anomalously developed human coronary sinus and cardiac veins. A wide range of morphological and experimental references was consulted in order to enable thorough discussion of the anatomical findings in the light of modern cardiological diagnostics and treatment. The anatomical and clinical nomenclature is presented and there is a brief comment on modern diagnostic techniques and their applications where the cardiac veins are concerned. The two principal and one compound cardiac venous system are defined and discussed with reference to the existence of both the normal and anomalous coronary sinus and cardiac vein. 1. The greater (major) cardiac venous system (2) The smaller (minor) cardiac venous system (3)The compound cardiac

  5. Murine myocardium OCT imaging with a blood substitute

    NASA Astrophysics Data System (ADS)

    Kim, Jeehyun; Villard, Joseph W.; Lee, Ho; Feldman, Marc D.; Milner, Thomas E.

    2002-06-01

    Imaging of the in vivo murine myocardium using optical coherence tomography (OCT) is described. Application of conventional techniques (e.g. MRI, Ultrasound imaging) for imaging the murine myocardium is problematic because the wall thickness is less than 1.5mm (20g mouse), and the heart rate can be as high as six-hundred beats per minute. To acquire a real-time image of the murine myocardium, OCT can provide sufficient spatial resolution (10 micrometers ) and imaging speed (1000 A-Scans/s). Strong light scattering by blood in the heart causes significant light attenuation making delineation of the endocardium-chamber boundary problematic. By replacing whole blood in the mouse with an artificial blood substitute we demonstrate significant reduction of light scattering in the murine myocardium. The results indicate a significant reduction in light scattering as whole blood hematocrit is diminished below 5%. To measure thickness change of the myocardium during one cycle, a myocardium edge detection algorithm is developed and demonstrated.

  6. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  7. Anisotropy of the Elastic Properties of Normal and Pathological Myocardium: Angular Dependence of Ultrasonic Backscatter, Attenuation, and Velocity.

    NASA Astrophysics Data System (ADS)

    Verdonk, Edward Dennis

    The focus of this thesis is the measurement of anisotropies in the ultrasonic parameters of soft tissues. The goal is to contribute to a better understanding of the physics which underlies the interaction of ultrasonic waves with inhomogeneous and anisotropic media. Broadband measurements using a piezoelectric transducer are reported for investigations of excised specimens of human and canine myocardial tissue. Emphasis is placed on identifying the effect that the muscle fiber orientation, relative to the direction of insonification, has on the propagation and scattering properties of ultrasonic waves. Results of the anisotropy of backscatter, the anisotropy of attenuation, and the anisotropy of quasilongitudinal velocity are presented for data obtained in 2^ circ increments through the full 360 ^circ relative to the myofibers. Measured velocities are used in conjunction with measured specimen densities to determine the elastic stiffness constants c_{11} and c_ {33} and to estimate specific mechanical moduli for thin layers of myocardium.

  8. Vaccines for Canine Leishmaniasis

    PubMed Central

    Palatnik-de-Sousa, Clarisa B.

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

  9. The Canine Oral Microbiome

    PubMed Central

    Dewhirst, Floyd E.; Klein, Erin A.; Thompson, Emily C.; Blanton, Jessica M.; Chen, Tsute; Milella, Lisa; Buckley, Catherine M. F.; Davis, Ian J.; Bennett, Marie-Lousie; Marshall-Jones, Zoe V.

    2012-01-01

    Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S rRNA-gene sequence comparison, shared between humans and dogs, two divergent mammalian species. Second, canine oral bacteria are of interest to veterinary and human medical communities for understanding their roles in health and infectious diseases. The bacteria involved are mostly unnamed and not linked by 16S rRNA-gene sequence identity to a taxonomic scheme. This manuscript describes the analysis of 5,958 16S rRNA-gene sequences from 65 clone libraries. Full length 16S rRNA reference sequences have been obtained for 353 canine bacterial taxa, which were placed in 14 bacterial phyla, 23 classes, 37 orders, 66 families, and 148 genera. Eighty percent of the taxa are currently unnamed. The bacterial taxa identified in dogs are markedly different from those of humans with only 16.4% of oral taxa are shared between dogs and humans based on a 98.5% 16S rRNA sequence similarity cutoff. This indicates that there is a large divergence in the bacteria comprising the oral microbiomes of divergent mammalian species. The historic practice of identifying animal associated bacteria based on phenotypic similarities to human bacteria is generally invalid. This report describes the diversity of the canine oral microbiome and provides a provisional 16S rRNA based taxonomic scheme for naming and identifying unnamed canine bacterial taxa. PMID:22558330

  10. Fatty acid uptake in normal human myocardium

    SciTech Connect

    Vyska, K.; Meyer, W.; Stremmel, W.; Notohamiprodjo, G.; Minami, K.; Machulla, H.J.; Gleichmann, U.; Meyer, H.; Koerfer, R. )

    1991-09-01

    Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 {plus minus} 0.024 mumol/g and 0.37 {plus minus} 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.

  11. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  12. Effect of angiotensin-induced hypertension on rat coronary arteries and myocardium.

    PubMed Central

    Giacomelli, F.; Anversa, P.; Wiener, J.

    1976-01-01

    Acute hypertension has been produced in rats by the intravenous infusion of angiotensin amide for 4 hours. Both control and hypertensive animals were injected intravenously prior to sacrifice with either horseradish peroxidase (HRP) or colloidal carbon. Epicardial arteries and blocks of ventricular myocardium containing intramyocardial arteries and arterioles have been processed for electron microscopy. HRP appears to penetrate the endoethelium of epicardial arteries from control animals within vesicles that bypass endothelial junctions and empty into interendoethelial clefts. Peroxidase does not traverse the endothelium of intramural arteries and arterioles of controls over the 10-minute period of observation. There is acceleration of lateral vesicular transport in the endothelium of epicardial arteries after angiotensin infusion and direct permeation of interendothelial clefts of intramural arterial vessels. Medial fragmentation and more extensive necrosis are observed in intramyocardial but not in epicardial arterial vessels. Foci of myocardial damage resembling irreversible ischemic or anoxic injury followed by reflow are described. It is suggested that the increased permeability of epicardial arteries may be due to elevated pressure, while the altered permeability and vascular lesions of intramural arteries and arterioles are more readily attributable to the vasoconstriction produced by angiotension. The vascular and myocardial lesions are also discussed in relation to the regional actions of angiotensin on the coronary circulation and known effects of this vasoactive peptide on myocardium. Images Figure 19 Figure 26 Figure 27 Figure 28 Figure 1 Figure 2 Figures 20 and 21 Figure 29 Figure 30 Figure 3 Figure 4 Figures 5-8 Figure 9 Figure 22 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 23 Figure 24 Figure 25 Figure 16 Figure 17 Figure 18 PMID:937512

  13. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts

    PubMed Central

    Gerbin, Kaytlyn A.; Yang, Xiulan; Murry, Charles E.; Coulombe, Kareen L. K.

    2015-01-01

    Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300–390 beats per minute (5–6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart’s pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of

  14. Diagnosis and prognosis of ischemic heart disease: the framework of cardiac magnetic resonance.

    PubMed

    Guaricci, Andrea Igoren; Brunetti, Natale Daniele; Marra, Martina Perazzolo; Tarantini, Giuseppe; di Biase, Matteo; Pontone, Gianluca

    2015-10-01

    Cardiac magnetic resonance is considered the gold standard in the evaluation of morphology, function, viability and tissue characterization owing to its high spatial resolution and excellent signal-to-noise ratio. Its accuracy and reproducibility, also thanks to steady-state free precession sequences allowing superior blood-myocardium delineation, are ascertained. Its current indications in the field of ischemic heart disease are multiple and continuously evolving. This technology can provide information on myocardium at risk, infarcted myocardium, microvascular obstruction and intramyocardial haemorrhage. The evaluation of each of these indexes has pivotal importance from a prognostic point of view. Rapid technological innovation engenders faster sequences and new contrast agents whereby a more accurate study of the myocardium and coronary artery disease is possible. On the contrary, there is the huge potentiality of noncontrast cardiac magnetic resonance that is especially appealing as a screening tool in asymptomatic younger patients because of radiation-free ionizing. Last but not the least, it is necessary to underline that the employment of cardiac magnetic resonance in clinical practice is restricted to few centres. This is mainly due to the need for a very high competence level and to the complexity of technical challenges required to industrial engineering, whereas the concerns expressed for its relatively high costs seem partly unfounded. PMID:25798902

  15. Canine degenerative myelopathy.

    PubMed

    Coates, Joan R; Wininger, Fred A

    2010-09-01

    Canine degenerative myelopathy (DM) is an adult-onset fatal neurodegenerative disease that occurs in many breeds. The initial upper motor neuron spastic paraparesis and general proprioceptive ataxia in the pelvic limbs progress to a flaccid lower motor neuron tetraparesis. Recently, a missense mutation in the superoxide dismutase 1 (SOD1) gene was found to be a risk factor for DM, suggesting that DM is similar to some forms of human amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). This article reviews the current knowledge of canine DM with regard to its signalment, clinical spectrum, diagnostic approach, and treatment. The implications of the SOD1 mutation on both diseases are discussed, comparing pathogenic mechanisms while conveying perspectives to translational medicine. PMID:20732599

  16. [The use of metabolic therapy in the treatment of ischemic heart disease in hemodynamically formed insignificant aortic stenosis with chronic heart failure].

    PubMed

    Kuriata, A V; Karavanskaia, I L; Kushnir, Iu S

    2011-01-01

    Analysis of medical treatment was conducted with justified using of the metabolic component in a complex therapy of ischemic heart disease with chronic heart failure in hemodynamically formed insignificant aortic stenoses. The effect of metabolic correction is shown for pharmaceutical compounds Meldoniya in the form of Vasonat manufactured by "OlainFarm" (Latvia). Positive results of maintenance of systolic activity and prevention of diastolic dysfunction of myocardium were presented. The application of Vasonat in appropriate for the stabilization of adaptive properties of the myocardium and prophylaxis of the development of critical indicators of heart failure in this combined. PMID:22768738

  17. Control of canine distemper.

    PubMed

    Chappuis, G

    1995-05-01

    Control of canine distemper can realistically only be achieved by the use of vaccination. The types of vaccine in current use are described, together with some of the problems encountered such as interference by maternal antibodies, and usage in species other than dogs. Modified live viral vaccines, as used for more than thirty years, have proved very effective. Nevertheless there is scope for some improvement in vaccine efficacy and recent developments in genetic recombinant methods are described. PMID:8588329

  18. Canine ehrlichiosis in Connecticut.

    PubMed Central

    Magnarelli, L A; Litwin, H J; Holland, C J; Anderson, J F; Ristic, M

    1990-01-01

    The first case of canine ehrlichiosis in Connecticut is reported. A female Brittany spaniel from Milford presented with lethargy, anorexia, fever, petechiae, splenomegaly, thrombocytopenia, anemia, elevated serum alkaline phosphatase, lymphopenia, and hypoalbuminemia. Serologic analysis revealed antibodies to Ehrlichia canis (titer, 1:2,560). This documents a more northern geographic distribution in the United States for this infectious agent than had previously been suspected. PMID:2312682

  19. American canine hepatozoonosis.

    PubMed

    Panciera, R J; Ewing, S A

    2003-06-01

    American canine hepatozoonosis is an emerging, tick-transmitted infection of domestic dogs caused by a recently recognized species of apicomplexan parasite, Hepatozoon americanum. The known definitive host of the protozoan is the Gulf Coast tick, Amblyomma maculatum. Presently recognized intermediate hosts include the domestic dog and the coyote, Canis latrans. Laboratory-reared larval or nymphal A. maculatum can be infected readily by feeding to repletion on a parasitemic intermediate host; sporogony requires 35-40 days. Transmission of infection to the dog has been produced experimentally by oral administration of mature oocysts or oocyst-containing ticks. Canine disease follows experimental exposure in 4-6 weeks and is characterized by systemic illness, extreme neutrophilic leukocytosis, muscle and bone pain, and proliferation of periosteal bone. Histopathological findings include multifocal skeletal and cardiac myositis associated with escape of mature merozoites from within the host-cell environment. There is also rapid onset of periosteal activation and osteogenesis and, less frequently, glomerulopathy and amyloidosis. Sequential stages of development of H. americanum in both the dog and the tick have been elucidated. Gamonts potentially infectious to ticks have been observed in peripheral blood leukocytes of the dog in as few as 28 days after exposure to oocysts. Young coyotes experimentally exposed to a canine strain of H. americanum acquired disease indistinguishable from that of similarly exposed young dogs. PMID:12885206

  20. Regional myocardial shape and dimensions of the working isolated canine left ventricle

    NASA Technical Reports Server (NTRS)

    Ritman, E.; Tsuiki, K.; Donald, D.; Wood, E. H.

    1975-01-01

    Angiographic experiments were performed on isolated canine left ventricle preparations using donor dog to supply blood to the coronary circulation via a rotary pump to control coronary flow. The angiographic record was transferred from video tape to video disk for detailed uninterrupted sequential analysis at a frequency of 60 fields/sec. It is shown that the use of a biplane X-ray technique and a metabolically supported isolated canine left ventricle preparation provides an angiographically ideal means of measuring the mechanical dynamics of the myocardium while the intact left ventricular myocardial structure and electrical activation pattern retain most of the in situ ventricular characteristics. In particular, biplane X-ray angiography of the left ventricle can provide estimates of total ventricular function such as ejection fraction, stroke volume, and myocardial mass correct to within 15% under the angiographically ideal conditions of the preparation.

  1. Lidocaine Enhances Contractile Function of Ischemic Myocardial Regions in Mouse Model of Sustained Myocardial Ischemia

    PubMed Central

    Kania, Gabriela; Osto, Elena; Jakob, Philipp; Krasniqi, Nazmi; Beck-Schimmer, Beatrice; Blyszczuk, Przemyslaw; Eriksson, Urs

    2016-01-01

    Rationale Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear. Methods Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12–16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements. Results Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium. Conclusion VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia. PMID:27140425

  2. Adenosine and Ischemic Preconditioning

    PubMed Central

    Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

    2012-01-01

    Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

  3. A Novel Canine Model of Acute Vertebral Artery Occlusion

    PubMed Central

    Zhang, Yunfeng; Jin, Min; Du, Bin; Lin, Hao; Xu, Chengyong; Jiang, Weijian; Jia, Jianping

    2015-01-01

    Background The extended time window and theoretic reduction in hemorrhage make mechanical strategies an attractive approach for the treatment of patients with ischemic stroke. However, a limited availability of suitable animal models of cerebrovascular thrombosis has hampered the study of novel endovascular interventions. The aim of the present study was to develop a new technique for site-specific placement of a thrombus in a canine model that would allow for the evaluation of mechanical thrombectomy and clot retrieval methods and the visualization of thrombus dislocation or fragmentation during angiographic manipulation. Methods Angiography and embolization with a preformed thrombus were performed in 12 canines. Under fluoroscopic guidance, an embolism protection device (EPD) was anchored to the middle segment of the left vertebral artery (VA) via the left femoral arterial sheath. A preformed radiopaque clot was injected through the guide catheter into the left VA, via the contralateral femoral artery, proximal to the EPD. After 15 min of occlusion, the EPD was removed and persistent occlusion of the VA was documented angiographically. Results Angiography performed during the observation period confirmed the persistence of VA occlusion in each case, and displacement of the radiopaque clots did not occur during the 3-hour observation period. The technique allowed selective embolization of targeted vessels without thrombus fragmentation. Conclusion This study demonstrates, for the first time, a canine model of post-circulation embolism induced by autologous blood clot placement. This model can be rapidly formed and easily operated, and the site of thrombosis can be readily controlled. PMID:26545253

  4. Cardiac MRI and Ischemic Heart Disease: Role in Diagnosis and Risk Stratification.

    PubMed

    Sawlani, Rahul N; Collins, Jeremy D

    2016-05-01

    Cardiac magnetic resonance imaging (CMRI) has been under development for the past four decades and has more recently become an essential tool in the evaluation of ischemic heart disease (IHD). It is the reference standard for quantification of both right and left ventricular volume and function and, after landmark work published in the New England Journal of Medicine in 2000, has proven effective in identifying hibernating myocardium, or hypokinetic myocardium that will recover after revascularization. More recent literature continues to support both delayed enhancement imaging and CMRI stress perfusion as essential tools in evaluating IHD. This review will briefly address the basics of CMRI and the scientific literature supporting the use of CMRI in IHD. It will then address more recent clinical studies establishing the clinical utility of CMRI in IHD, followed by a discussion of future directions in CMRI. PMID:26980317

  5. Ginsenoside-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis in rats

    PubMed Central

    LIU, XIAOMIN; JIANG, YICHUAN; YU, XIAOFENG; FU, WENWEN; ZHANG, HONG; SUI, DAYUN

    2014-01-01

    Ginsenoside-Rb3 (G-Rb3) has been previously demonstrated to attenuate myocardial ischemia-reperfusion injury (MIRI). The aim of the present study was to investigate this further and determine whether G-Rb3 protects the myocardium from ischemia-reperfusion injury via the inhibition of apoptosis. Adult male Sprague Dawley rats were randomly divided into four groups: Sham, MIRI, G-Rb3 treatment (orally, 20 mg/kg) and ischemic postconditioning (as the positive control). The drug or placebo treatment was administered to the rats once a day for three consecutive days, and MIRI was then induced by subjecting the rats to left anterior descending coronary artery ligation for 30 min and reperfusion for 2 h. The results showed that G-Rb3 treatment significantly reduced the number of apoptotic cells in the myocardium and the expression of B-cell lymphoma 2-associated X protein, and increased the expression of B-cell lymphoma 2. The activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-MB in the serum were also reduced significantly by the G-Rb3 treatment. These findings suggest that G-Rb3 inhibits apoptosis in the early stage of MIRI, and attenuates MIRI when the reperfusion continues. G-Rb3 was also shown to significantly reduce the level of malondialdehyde and increase the activity of superoxide dismutase in the myocardium, which suggests that attenuating reactive oxygen species accumulation and oxidative stress may be the major mechanism underlying the anti-apoptotic effects of G-Rb3. The release of inflammatory factors was significantly attenuated by G-Rb3, which may also be associated with its anti-apoptotic effects. PMID:25371727

  6. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    PubMed Central

    Zhu, Kai; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Wang, Lingyan; Wang, Chunsheng

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. PMID:25429216

  7. System of scale-selective tomography of myocardium birefringence

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Ushenko, Yu. O.; Dubolazov, O. V.; Savich, V. O.

    2015-09-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  8. Stem cell implantation in ischemic mouse heart: a high-resolution magnetic resonance imaging investigation.

    PubMed

    Küstermann, Ekkehard; Roell, Wilhelm; Breitbach, Martin; Wecker, Stefan; Wiedermann, Dirk; Buehrle, Christian; Welz, Armin; Hescheler, Juergen; Fleischmann, Bernd K; Hoehn, Mathias

    2005-10-01

    Advances in the biology of stem cells have evoked great interest in cell replacement therapies for the regeneration of heart tissue after myocardial infarction. However, results from human trials are controversial, since the destination of the injected cells, their engraftment and their long-term fate have remained unclear. Here we investigate whether transplanted cells can be identified in the intact and lesioned murine myocardium employing high-resolution MRI. Cardiac progenitor cells, expressing the enhanced green fluorescent protein (EGFP), were labeled with ultra-small paramagnetic iron-oxide (USPIO) nanoparticles and transplanted into the intact or injured myocardium of mice. Their precise location was determined with high-resolution MRI and compared with histological tissue sections, stained with Prussian blue for iron content. These experiments showed that iron nanoparticle-loaded cells could be identified at high resolution in the mouse heart. However, ischemic myocardium (after cryoinjury or left coronary artery ligation) was characterized by a signal attenuation similar to that induced by USPIO-labeled cells in T2*-weighted MR images, making detection of labeled stem cells in this area by T2*-sensitive contrast rather difficult. In animals with myocardial injury only, the signal attenuated areas were of the same size in proton density- and T2*-weighted MR images. In injured animals also receiving labeled cells the lesioned area appeared larger in T2*--than in proton density-weighted MR images. This sequence-dependent lesion size change is due to the increased signal loss caused by the iron oxide nanoparticles, most sensitively detectable in the T2*-sensitive images. Thus, using the novel combination of these two parameter weightings, USPIO-labeled cells can be detected at high resolution in ischemic myocardium. PMID:15948224

  9. Myocardial ischemic reperfusion induces de novo Nrf2 protein translation

    PubMed Central

    Xu, Beibei; Zhang, Jack; Strom, Joshua; Lee, Sang; Chen, Qin M.

    2016-01-01

    Nrf2 is a bZIP transcription factor regulating the expression of antioxidant and detoxification genes. We have found that Nrf2 knockout mice have an increased infarction size in response to regional ischemic reperfusion and have a reduced degree of cardiac protection by means of ischemic preconditioning. With cycles of brief ischemia and reperfusion (5′I/5′R) that induce cardiac protection in wild type mice, an elevated Nrf2 protein was observed without prior increases of Nrf2 mRNA. When an mRNA species is being translated into a protein, it is occupied by multiple ribosomes. The level of ribosome-associated Nrf2 mRNA increased following cycles of 5′I/5′R, supporting de novo Nrf2 protein translation. A dicistronic reporter assay indicated a role of the 5′ untranslated region (5′ UTR) of Nrf2 mRNA in oxidative stress induced Nrf2 protein translation in isolated cardiomyocytes. Western blot analyses after isolation of proteins binding to biotinylated Nrf2 5′ UTR from the myocardium or cultured cardiomyocytes demonstrated that cycles of 5′I/5′R or oxidants caused an increased association of La protein with Nrf2 5′ UTR. Ribonucleoprotein complex immunoprecipitation assays confirmed such association indeed occurring in vivo. Knocking down La using siRNA was able to prevent Nrf2 protein elevation by oxidants in cultured cardiomyocytes and by cycles of 5′I/5′R in the myocardium. Our data point out a novel mechanism of cardiac protection by de novo Nrf2 protein translation involving interaction of La protein with 5′ UTR of Nrf2 mRNA in cardiomyocytes. PMID:24915518

  10. Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells

    PubMed Central

    Lachtermacher, Stephan; Esporcatte, Bruno L. B.; da Silva de Azevedo Fortes, Fábio; Rocha, Nazareth Novaes; Montalvão, Fabrício; Costa, Patricia C.; Belem, Luciano; Rabischoffisky, Arnaldo; Neto, Hugo C. C. Faria; Vasconcellos, Rita; Iacobas, Dumitru A.; Iacobas, Sanda; Spray, David C.; Thomas, Neil M.; Goldenberg, Regina C. S.; de Carvalho, Antonio C. Campos

    2011-01-01

    Although bone marrow-derived mononuclear cells (BMNC) have been extensively used in cell therapy for cardiac diseases, little mechanistic information is available to support reports of their efficacy. To address this shortcoming, we compared structural and functional recovery and associated global gene expression profiles in post-ischaemic myocardium treated with BMNC transplantation. BMNC suspensions were injected into cardiac scar tissue 10 days after experimental myocardial infarction. Six weeks later, mice undergoing BMNC therapy were found to have normalized antibody repertoire and improved cardiac performance measured by ECG, treadmill exercise time and echocardiography. After functional testing, gene expression profiles in cardiac tissue were evaluated using high-density oligonucleotide arrays. Expression of more than 18% of the 11981 quantified unigenes was significantly altered in the infarcted hearts. BMNC therapy restored expression of 2099 (96.2%) of the genes that were altered by infarction but led to altered expression of 286 other genes, considered to be a side effect of the treatment. Transcriptional therapeutic efficacy, a metric calculated using a formula that incorporates both recovery and side effect of treatment, was 73%. In conclusion, our results confirm a beneficial role for bone marrow-derived cell therapy and provide new information on molecular mechanisms operating after BMNC transplantation on post ischemic heart failure in mice. PMID:21671060

  11. [Effect of adaptation to hypoxia on expression of NO synthase isoforms in rat myocardium].

    PubMed

    Goryacheva, A V; Terekhina, O L; Abramochkin, D V; Budanova, O P; Belkina, L M; Smirin, B V; Downey, H F; Malyshev, I Yu; Manukhina, E B

    2015-01-01

    Previously we have shown that adaptation to hypoxia (AH) is cardio- and vasoprotective in myocardial ischemic and reperfusion injury and this protection is associated with restriction of nitrosative stress. The present study was focused on further elucidation of NO-dependent mechanisms of AH by identifying specific NO synthases (NOS) that could play the major role in AH protection. AH was performed in a normobaric hypoxic chamber by breathing hypoxic gas mixture (9.5-10% O2) for 5-10 min with intervening 4 min normoxia (5-8 cycles daily for 21 days). Expression of neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) protein was measured in the left ventricular myocardium using Western blot analysis with respective antibodies. AH educed iNOS protein expression by 71% (p < 0.05) whereas eNOS protein expression tended to be reduced by 41% compared to control (p < 0.05). nNOS protein expression remained unchanged after AH. Selective iNOS inhibition can mimic the AH-induced protection. Therefore protective effects of AH could be at least partially due to restriction of iNOS and, probably, eNOS expression. PMID:27116881

  12. Three-dimensional imaging of the myocardium with isotopes

    NASA Technical Reports Server (NTRS)

    Budinger, T. F.

    1975-01-01

    Three methods of imaging the three-dimensional distribution of isotopes in the myocardium are discussed. Three-dimensional imaging was examined using multiple Anger-camera views. Longitudinal tomographic images with compensation for blurring were studied. Transverse-section reconstruction using coincidence detection of annihilation gammas from positron emitting isotopes was investigated.

  13. Stereology of the myocardium in Leontopithecus (Lesson, 1840) callitrichidae - primates.

    PubMed

    Pissinatti, A; Burity, C H F; Mandarim-de-Lacerda, C A

    2003-06-01

    Rare morphological features of the Leontopithecus cardiovascular system have been reported in the literature. The samples analyzed in this study came from 33 specimens of Leontopithecus from the collection of the Center of Primatology of Rio de Janeiro-FEEMA (CPRJ-FEEMA). Morphometry and stereological data were obtained from all animals. Adult body weights of L. rosalia were the lowest, the greatest being those of L. chrysopygus caissara; body weights of L. chrysomelas and L. c. chrysopygus were similar and in between those of the two former species. Cardiomyocytes (left ventricular myocardium) were bigger in adults than in infants. The myocardium of L. rosalia showed focal fibrosis, fatty vacuoles, and hyalinization. In L. chrysomelas the myocardium showed areas of fibrosis and presence of mononuclear cells. Fibrosis and areas of congestion were observed in L. c. chrysopygus; areas of disorganization and vascular congestion were found in L. c. caissara. In L. rosalia infants, a greater density of vessels per myocardial area and a greater length density of vessels were observed as compared with those of L. chrysomelas. In adults, L. chrysomelas showed greater density of connective tissue in the myocardium than L. c. chrysopygus and L. c. caissara did. In L. rosalia, cardiomyocyte nuclei had a greater area density than those of the other forms of Leontopithecus. These characteristics may explain the faster development of L. rosalia infants as compared with that of L. chrysomelas and L. c. chrysopygus kept under the same handling conditions at the CPRJ-FEEMA. PMID:12823624

  14. Canine mast cell tumors.

    PubMed

    Macy, D W

    1985-07-01

    Despite the fact that the mast cell tumor is a common neoplasm of the dog, we still have only a meager understanding of its etiology and biologic behavior. Many of the published recommendations for treatment are based on opinion rather than facts derived from careful studies and should be viewed with some skepticism. Because of the infrequent occurrence of this tumor in man, only a limited amount of help can be expected from human oncologists; therefore, burden of responsibility for progress in predicting behavior and developing treatment effective for canine mast cell tumors must fall on the shoulders of the veterinary profession. PMID:3929444

  15. Brazilian canine hepatozoonosis.

    PubMed

    O'Dwyer, Lucia Helena

    2011-01-01

    The genus Hepatozoon includes hundreds of species that infect birds, reptiles, amphibians and mammals, in all continents with tropical and subtropical climates. Two species have been described in domestic dogs: H. canis, reported in Europe, Asia, Africa, South America and the United States; and H. americanum, which so far has only been diagnosed in the United States. In Brazil, the only species found infecting dogs is H. canis. The objective of this review was to detail some aspects of canine hepatozoonosis, caused by H. canis, and the main points of its biology, transmission, pathogenicity, symptoms, epidemiology and diagnostic methods, with emphasis on research developed in Brazil. PMID:21961746

  16. Absence of canine papillomavirus sequences in canine mammary tumours.

    PubMed

    Sardon, D; Blundell, R; Burrai, G P; Alberti, A; Tore, G; Passino, E Sanna; Antuofermo, E

    2015-01-01

    Human papillomaviruses (PVs) are found in human breast cancer tissue; however, it remains controversial as to whether these viruses play a role in the aetiology of this tumour. There has been minimal study of whether PVs are found in normal or abnormal mammary glands of animals. The present study investigated whether a PV sequence could be found in the mammary glands of 33 female dogs by rolling circle amplification and polymerase chain reaction. No PV DNA was found in normal or neoplastic canine mammary tissues, suggesting that canine PVs are probably not involved in the pathogenesis of canine mammary neoplasia. PMID:25435511

  17. Identification of Ischemic Lesions Based on Difference Integral Maps, Comparison of Several ECG Intervals

    NASA Astrophysics Data System (ADS)

    Švehlíková, J.; Kania, M.; Turzová, M.; Hebláková, E.; Tyšler, M.; Maniewski, R.

    2009-01-01

    Ischemic changes in small areas of myocardium can be detected from difference integral maps computed from body surface potentials measured on the same subject in situations with and without manifestation of ischemia. The proposed method for their detection is the inverse solution with 2 dipoles. Surface potentials were recorded at rest and during stress on 10 patients and 3 healthy subjects. Difference integral maps were computed for 4 intervals of integration of electrocardiographic signal (QRST, QRSU, STT and STU) and their properties and applicability as input data for inverse identification of ischemic lesions were compared. The results showed that better (more reliable) inverse solutions can be obtained from difference integral maps computed either from QRST or from STT interval of integration. The average correlation between these maps was 97%. The use of the end of U wave instead of the end of T wave for interval of integration did not improve the results.

  18. Risk Stratification for Sudden Cardiac Death In Patients With Non-ischemic Dilated Cardiomyopathy

    PubMed Central

    Shekha, Karthik; Ghosh, Joydeep; Thekkoott, Deepak; Greenberg, Yisachar

    2005-01-01

    Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge .Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice. PMID:16943952

  19. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy

    PubMed Central

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34+ and CD 133+ stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future. PMID:26101528

  20. Protective effects of remote ischemic preconditioning in isolated rat hearts

    PubMed Central

    Teng, Xiao; Yuan, Xin; Tang, Yue; Shi, Jingqian

    2015-01-01

    To use Langendorff model to investigate whether remote ischemic preconditioning (RIPC) attenuates post-ischemic mechanical dysfunction on isolated rat heart and to explore possible mechanisms. SD rats were randomly divided into RIPC group, RIPC + norepinephrine (NE) depletion group, RIPC + pertussis toxin (PTX) pretreatment group, ischemia/reperfusion group without treatment (ischemia group) and time control (TC) group. RIPC was achieved through interrupted occlusion of anterior mesenteric artery. Then, Langendorff model was established using routine methods. Heart function was tested; immunohistochemistry and ELISA methods were used to detect various indices related to myocardial injury. Compared with ischemia group in which the hemodynamic parameters deteriorated significantly, heart function recovered to a certain degree among the RIPC, RIPC + NE depletion, and RIPC + PTX groups (P<0.05). More apoptotic nuclei were observed in ischemia group than in the other three groups (P<0.05); more apoptotic nuclei were detected in NE depletion and PTX groups than in RIPC group (P<0.05). While, there was no significant difference between NE depletion and PTX groups. In conclusion, RIPC protection on I/R myocardium extends to the period after hearts are isolated. NE and PTX-sensitive inhibitory G protein might have a role in the protection process. PMID:26550168

  1. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672

  2. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    SciTech Connect

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalen; Palmqvist, Lars; Jeppsson, Anders; Hulten, Lillemor Mattsson

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

  3. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection

    PubMed Central

    Cowan, Douglas B.; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R.; Thedsanamoorthy, Jerusha K.; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; del Nido, Pedro J.; Packard, Alan B.

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  4. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection.

    PubMed

    Cowan, Douglas B; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R; Thedsanamoorthy, Jerusha K; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; Del Nido, Pedro J; Packard, Alan B; McCully, James D

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  5. Canine rickettsial infections.

    PubMed

    Stiles, J

    2000-09-01

    Dogs that live in tick-infested areas are at risk for contracting rickettsial infections. Clinical signs associated with ehrlichiosis or Rocky Mountain spotted fever may be dramatic or mild. Clinicians must consider the possibility of rickettsial diseases to request laboratory tests that will permit a proper diagnosis. Specific antimicrobial therapy usually brings about clinical improvement, although some dogs may not be cleared of rickettsial organisms, even with prolonged treatment. A small percentage of dogs die of rickettsial infections, either in the acute stage or owing to chronic bone marrow suppression and generalized debilitation. Ocular lesions are an important clinical sign in canine rickettsial infections and may aid the clinician in making a diagnosis and monitoring response to therapy. PMID:11033879

  6. Canine cutaneous leishmaniasis.

    PubMed

    Sasani, F; Javanbakht, J; Samani, R; Shirani, D

    2016-03-01

    Canine cutaneous leishmaniasis (CCL) is a significant veterinary problem. Infected dogs also serve as parasite reservoirs and contribute to human transmission of cutaneous leishmaniasis. Histologically, the lesions were nodular to diffuse interstitial granulomatous dermatitis with histiocytic pseudorosettes together with numerous amastigotes within macrophages and occasionally within the interstitium. Organisms were often contained within clear and intracellular vacuoles. The other inflammatory cells, which were present in the biopsies of the Leishmania-infected dog, were lymphocytes and plasma cells. The histopathology results emphasized the role of dog, particularly asymptomatic dog, as reservoirs for CCL because of the high cutaneous parasite loads. These results may help to explain the maintenance of high transmission rates and numbers of CCL cases in endemic urban regions. PMID:27065598

  7. Influence of viscosity on myocardium mechanical activity: a mathematical model.

    PubMed

    Katsnelson, Leonid B; Nikitina, Larissa V; Chemla, Denis; Solovyova, Olga; Coirault, Catherine; Lecarpentier, Yves; Markhasin, Vladimir S

    2004-10-01

    We have previously proposed and validated a mathematical model of myocardium contraction-relaxation cycle based on current knowledge of regulatory role of Ca2+ and cross-bridge kinetics in cardiac cell. That model did not include viscous elements. Here we propose a modification of the model, in which two viscous elements are added, one in parallel to the contractile element, and one more in parallel to the series elastic element. The modified model allowed us to simulate and explain some subtle experimental data on relaxation velocity in isotonic twitches and on a mismatch between the time course of sarcomere shortening/lengthening and the time course of active force generation in isometric twitches. Model results were compared with experimental data obtained from 28 rat LV papillary muscles contracting and relaxing against various loads. Additional model analysis suggested contribution of viscosity to main inotropic and lusitropic characteristics of myocardium performance. PMID:15302547

  8. Acute Ischemic Stroke Intervention.

    PubMed

    Khandelwal, Priyank; Yavagal, Dileep R; Sacco, Ralph L

    2016-06-01

    Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID:27256835

  9. Remote Ischemic Conditioning

    PubMed Central

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  10. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke. PMID:23805635

  11. Oxygen diffusion distance in thyroxine-induced hypertrophic rabbit myocardium.

    PubMed

    Seiden, D; Navidad, P; Weiss, H R

    1988-10-01

    We studied the oxygen diffusion distance in the rabbit myocardium in untreated animals and in animals treated with thyroxine (T4) for 3 days and 16 days. The subepicardial and subendocardial regions were studied separately. Sixteen days of T4 treatment results in significant cardiac hypertrophy. After 16 days, the percentage of the myocardium occupied by myocytes decreases as the volume of extracellular matrix increases. After 3 days, the number of myocyte mitochondria per unit volume of myocardium increases without an increase in mitochondrial volume. After 16 days the volume density of the myocyte mitochondria increases. Oxygen diffusion distance was determined by measuring the distance between the myocardial capillaries and the cardiomyocyte mitochondria. The deposition of extracellular matrix results in an increase in the distance between the myocardial capillaries and the myocytes. The distribution of the mitochondria within the myocytes remains unchanged resulting in an increased distance between the capillaries and the mitochondria, hence, an increased oxygen diffusion distance. There is some evidence that the mitochondria most distant from the capillaries are the mitochondria in which division is most frequent with T4 stimulation. This may be related to the relative deprivation of oxygen of these mitochondria. PMID:2975340

  12. Direct effects of smoking on the heart: silent ischemic disturbances of coronary flow

    SciTech Connect

    Deanfield, J.E.; Shea, M.J.; Wilson, R.A.; Horlock, P.; de Landsheere, C.M.; Selwyn, A.P.

    1986-05-01

    Cigarette smoking is strongly associated with ischemic heart disease and acute coronary events. The effect of smoking a single cigarette on regional myocardial perfusion was studied in 13 chronic smokers with typical stable angina pectoris using positron emission tomography and rubidium-82 (/sup 82/Rb). Findings were compared with the effects of physical exercise. After exercise, 8 patients (61%) had angina, ST depression and abnormal regional myocardial perfusion. Uptake of /sup 82/Rb increased from 49 +/- 8 to 60 +/- 7 in remote myocardium, but decreased from 46 +/- 3 to 37 +/- 5 in an ischemic area. The remaining 5 patients (39%) had homogeneous increases in /sup 82/Rb uptake without angina or ST depression. After smoking, 6 of the 8 patients with positive exercise test responses had a decrease in /sup 82/Rb uptake, from 47 +/- 3 to 35 +/- 6 in the same segment of myocardium affected during exercise. However, in contrast to exercise, the events during smoking were largely silent. The absolute decreases in regional /sup 82/Rb uptake after smoking occurred at significantly lower levels of myocardial oxygen demand than after exercise. This suggests that an impairment of coronary blood supply is responsible. Thus, in smokers with coronary artery disease, each cigarette can cause profound silent disturbances of regional myocardial perfusion that are likely to occur frequently during daily life. Such repeated insults may represent an important mechanism linking smoking with coronary events.

  13. Ischemic ulcers - self-care

    MedlinePlus

    ... restrict blood flow. Certain lifestyle changes can help prevent ischemic ulcers. If you have a wound, taking these steps can improve blood flow and aid healing. Quit smoking. Smoking can lead to clogged arteries. ...

  14. BRAF Mutations in Canine Cancers

    PubMed Central

    Mochizuki, Hiroyuki; Kennedy, Katherine; Shapiro, Susan G.; Breen, Matthew

    2015-01-01

    Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated BRAF gene, this mutation has not yet been characterized in canine cancers. As human and canine cancers share molecular abnormalities, we hypothesized that BRAF gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of BRAF, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a single nucleotide T to A transversion at nucleotide 1349 occurred in 64 primary tumors (9.6%), with particularly high frequency in prostatic carcinoma (20/25, 80%) and urothelial carcinoma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for valine at codon 450 (V450E) of canine BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers. PMID:26053201

  15. Canine leishmaniosis in South America

    PubMed Central

    Dantas-Torres, Filipe

    2009-01-01

    Canine leishmaniosis is widespread in South America, where a number of Leishmania species have been isolated or molecularly characterised from dogs. Most cases of canine leishmaniosis are caused by Leishmania infantum (syn. Leishmania chagasi) and Leishmania braziliensis. The only well-established vector of Leishmania parasites to dogs in South America is Lutzomyia longipalpis, the main vector of L. infantum, but many other phlebotomine sandfly species might be involved. For quite some time, canine leishmaniosis has been regarded as a rural disease, but nowadays it is well-established in large urbanised areas. Serological investigations reveal that the prevalence of anti-Leishmania antibodies in dogs might reach more than 50%, being as high as 75% in highly endemic foci. Many aspects related to the epidemiology of canine leishmaniosis (e.g., factors increasing the risk disease development) in some South American countries other than Brazil are poorly understood and should be further studied. A better understanding of the epidemiology of canine leishmaniosis in South America would be helpful to design sustainable control and prevention strategies against Leishmania infection in both dogs and humans. PMID:19426440

  16. Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion.

    PubMed

    Brand, T; Sharma, H S; Fleischmann, K E; Duncker, D J; McFalls, E O; Verdouw, P D; Schaper, W

    1992-12-01

    The molecular basis of myocardial adaptation to ischemia and reperfusion is poorly understood. It is thought that nuclear proto-oncogenes act as third messengers, converting cytoplasmic signal transduction into long-term changes of gene expression. We studied the expression of six nuclear proto-oncogenes (Egr-1, c-fos, fosB, c-jun, junB, and c-myc) in myocardium subjected to ischemia and reperfusion in anesthetized pigs. Stunning was achieved by two 10-minute left anterior descending coronary artery occlusions separated by 30 minutes of reperfusion. Hearts were excised after the first occlusion, after the first reperfusion, and at 30, 120, 150, and 210 minutes of reperfusion after the second occlusion. Total RNA was prepared from stunned as well as normally perfused myocardial tissue and subjected to Northern blotting. The response of the six nuclear proto-oncogenes varied.fosB gene expression was never detected. The c-myc gene was expressed, but its level was unchanged by ischemia. c-jun expression was slightly increased by ischemia (3.1 +/- 0.6-fold). The c-fos, Egr-1, and junB genes were highly induced, being fivefold to sevenfold higher in experimental than in control tissue. In three animals pretreated with the beta 1-antagonist metoprolol and then subjected to the above experimental protocol, the induction of proto-oncogenes was similar to that in nonblocked controls. Our results show that the myocardial adaptive response to ischemic stress includes the induction of at least four transcription factors that may be further operative in repair processes and angiogenesis. PMID:1385005

  17. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

    PubMed

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

  18. [The effect of helium-neon laser radiation on the energy metabolic indices of the myocardium].

    PubMed

    Chizhov, G K; Koval'skaia, N I; Kozlov, V I

    1991-03-01

    It was shown in experiments on white rats, that intravenous and direct myocardium helium-neon laser irradiation leads to the some activation of lactate, glucose-6-phosphate, succinate and reduced NAD degydrogenases. During direct myocardium irradiation these changes are in a less degree. It is suggested that helium-neon laser irradiation displays some active influence on the energy metabolism enzymes of the myocardium, and the mechanisms of this action are discussed. PMID:2054512

  19. Improving the efficacy of therapeutic angiogenesis by UTMD-mediated Ang-1 gene delivery to the infarcted myocardium

    PubMed Central

    DENG, QING; HU, BO; CAO, SHENG; SONG, HONG-NING; CHEN, JIN-LING; ZHOU, QING

    2015-01-01

    This study aimed to verify the feasibility and efficacy of ultrasound-targeted microbubble destruction (UTMD)-mediated angiopoietin-1 (Ang-1) gene delivery into the infarcted myocardium. Microbubbles carrying anti-intercellular adhesion molecule-1 (ICAM-1) antibody were prepared and identified. The microbubbles carrying anti-ICAM-1 antibody selectively adhered to the interleukin (IL)-1β-stimulated ECV304 cells and to the ischemic vascular endothelium, and the infarct area was examined to evaluate the targeting ability of ICAM-1 microbubbles in vitro and in vivo. The intravenous administration of the Ang-1 gene was carried out by UTMD in rabbits with acute myocardial infarction (AMI). The rabbits were divided into the control (no treatment), non-targeted microbubble destruction (non-TMB) and the ICAM-1 TMB (TMB) group. Gene delivery by direct intramyocardial injection (IMI) served as a reference. Two weeks later, regional myocardial perfusion and cardiac function were evaluated by echocardiography, and Ang-1 gene-mediated angiogenesis was assessed histologically and biochemically. The results revealed that the ICAM-1-targeted microbubbles selectively adhered to the IL-1β-stimulated ECV304 cells in vitro and to the ischemic vascular endothelium in the infarct area of the rabbits with AMI. Two weeks after the delivery of the Ang-1 gene, compared with the non-TMB group, left ventricular function and myocardial perfusion at the infarct area had improved in the TMB and IMI group (p<0.01). Ang-1 gene expression was detectable in the non-TMB, TMB and IMI group, while its expression was higher in the latter 2 groups (all p<0.01). The microvascular density (MVD) of the infarct area in the non-TMB, TMB and IMI group was 65.6±4.4, 96.7±2.1 and 100.7±3.6, respectively (p<0.01). The findings of our study indicate that UTMD-mediated gene delivery may be used to successfully deliver the Ang-1 gene to the infarcted myocardium, thus improving the efficacy of therapeutic

  20. Molecular cloning and characterization of canine ICOS.

    PubMed

    Lee, Je-Hwan; Joo, Young-Don; Yim, Daesong; Lee, Richard; Ostrander, Elaine A; Loretz, Carol; Little, Marie-Térèse; Storb, Rainer; Kuhr, Christian S

    2004-10-01

    Inducible costimulatory receptor (ICOS) is one recently identified member of the CD28 family of costimulatory molecules. Evidence suggests ICOS functions as a critical immune regulator and, to evaluate these effects, we employed the canine model system that has been used to develop strategies currently in clinical use for hematopoietic stem cell transplantation. To investigate the effects of blocking the ICOS pathway in the canine hematopoietic cell transplantation model, we tested existing murine and human reagents and cloned the full length of the open reading frame of canine ICOS cDNA to allow the development of reagents specific for the canine ICOS. Canine ICOS contains a major open reading frame of 624 nucleotides, encoding a protein of 208 amino acids, and localizes to chromosome 37. Canine ICOS shares 79% sequence identity with human ICOS, 70% with mouse, and 69% with rat. Canine ICOS expression is limited to stimulated PBMC. PMID:15475250

  1. Myocardium proteome remodelling after nutritional deprivation of methyl donors.

    PubMed

    Martinez, Emilie; Gérard, Nicolas; Garcia, Maira M; Mazur, Andrzej; Guéant-Rodriguez, Rosa-Maria; Comte, Blandine; Guéant, Jean-Louis; Brachet, Patrick

    2013-07-01

    Methyl donor (MD: folate, vitamin B12 and choline) deficiency causes hyperhomocysteinemia, a risk factor for cardiovascular diseases. However, the mechanisms of the association between MD deficiency, hyperhomocysteinemia, and cardiomyopathy remain unclear. Therefore, we performed a proteomic analysis of myocardium of pups from rat dams fed a MD-depleted diet to understand the impact of MD deficiency on heart at the protein level. Two-dimension gel electrophoresis and mass spectrometry-based analyses allowed us to identify 39 proteins with significantly altered abundance in MD-deficient myocardium. Ingenuity Pathway Analysis showed that 87% of them fitted to a single protein network associated with developmental disorder, cellular compromise and lipid metabolism. Concurrently increased protein carbonylation, the major oxidative post-translational protein modification, could contribute to the decreased abundance of many myocardial proteins after MD deficiency. To decipher the effect of MD deficiency on the abundance of specific proteins identified in vivo, we developed an in vitro model using the cardiomyoblast cell line H9c2. After a 4-day exposure to a MD-deprived (vs. complete) medium, cells were deficient of folate and vitamin B12, and released abnormal amounts of homocysteine. Western blot analyses of pup myocardium and H9c2 cells yielded similar findings for several proteins. Of specific interest is the result showing increased and decreased abundances of prohibitin and α-crystallin B, respectively, which underlines mitochondrial injury and endoplasmic reticulum stress within MD deficiency. The in vitro findings validate the MD-deficient H9c2 cells as a relevant model for studying mechanisms of the early metabolic changes occurring in cardiac cells after MD deprivation. PMID:23318136

  2. Neurogenic stunned myocardium and cardiac transplantation: a case report.

    PubMed

    Hernández-Caballero, C; Martín-Bermúdez, R; Revuelto-Rey, J; Aguilar-Cabello, M; Villar-Gallardo, J

    2012-09-01

    We present the case of a 46-year-old woman referred to our center for urgent heart transplantation assessment, initially diagnosed as having cardiogenic shock of uncertain etiology. Some hours before she had suffered syncope without regaining consciousness. When she arrived at our hospital, the objective examination revealed bilateral unreactive mydriasis and absent brain-stem reflexes, and echocardiography showed global left ventricle wall hypokinesis sparing the apex. An urgent computed tomography (CT) imaging of the head was performed, which showed a massive subarachnoid hemorrhage and extensive cerebral edema. In the following hours, she fulfilled the criteria of brain-stem death and indeed became a multiorgan donor. The heart was rejected for transplantation because of the existence of left ventricle wall motion abnormalities associated with neurogenic stunned myocardium. Neurogenic stunned myocardium is a stress-related cardiomyopathy that occurs after an acute brain injury. It is especially frequent in subarachnoid hemorrhage, where it reaches an incidence of up to 40% of patients. It is characterized by acute electrocardiographic changes and regional hypokinesis of the left ventricle wall not consistent with the coronary artery distribution, and is thought to be a transient condition. For this reason it should not constitute an absolute contraindication to cardiac donation in young donors with no previous cardiac disease. In our hospital during the last year one third of the potential heart donors had regional left ventricle wall motion abnormalities compatible with neurogenic stunned myocardium. With the aim of improving the number of cardiac donors, several strategies have been described to try to demonstrate the reversibility of this entity, such as dobutamine stress echocardiography. PMID:22974925

  3. Ischemic Stroke after Heart Transplantation

    PubMed Central

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-01-01

    Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504

  4. Ischemic Stroke after Heart Transplantation.

    PubMed

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-05-01

    Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504

  5. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

    PubMed

    Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

    2015-03-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI. PMID:25750747

  6. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development☆

    PubMed Central

    Abd El Aziz, M.T.; Abd El Nabi, E.A.; Abd El Hamid, M.; Sabry, D.; Atta, H.M.; Rahed, L.A.; Shamaa, A.; Mahfouz, S.; Taha, F.M.; Elrefaay, S.; Gharib, D.M.; Elsetohy, Khaled A.

    2013-01-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI. PMID:25750747

  7. Statins Enhance Clonal Growth of Late Outgrowth Endothelial Progenitors and Increase Myocardial Capillary Density in the Chronically Ischemic Heart

    PubMed Central

    Wang, Wen; Lang, Jennifer K.; Suzuki, Gen; Canty, John M.; Cimato, Thomas

    2011-01-01

    Background Coronary artery disease and ischemic heart disease are leading causes of heart failure and death. Reduced blood flow to heart tissue leads to decreased heart function and symptoms of heart failure. Therapies to improve heart function in chronic coronary artery disease are important to identify. HMG-CoA reductase inhibitors (statins) are an important therapy for prevention of coronary artery disease, but also have non-cholesterol lowering effects. Our prior work showed that pravastatin improves contractile function in the chronically ischemic heart in pigs. Endothelial progenitor cells are a potential source of new blood vessels in ischemic tissues. While statins are known to increase the number of early outgrowth endothelial progenitor cells, their effects on late outgrowth endothelial progenitor cells (LOEPCs) and capillary density in ischemic heart tissue are not known. We hypothesized that statins exert positive effects on the mobilization and growth of late outgrowth EPCs, and capillary density in ischemic heart tissue. Methodology/Principal Findings We determined the effects of statins on the mobilization and growth of late outgrowth endothelial progenitor cells from pigs. We also determined the density of capillaries in myocardial tissue in pigs with chronic myocardial ischemia with or without treatment with pravastatin. Pravastatin therapy resulted in greater than two-fold increase in CD31+ LOEPCs versus untreated animals. Addition of pravastatin or simvastatin to blood mononuclear cells increased the number of LOEPCs greater than three fold in culture. Finally, in animals with chronic myocardial ischemia, pravastatin increased capillary density 46%. Conclusions Statins promote the derivation, mobilization, and clonal growth of LOEPCs. Pravastatin therapy in vivo increases myocardial capillary density in chronically ischemic myocardium, providing an in vivo correlate for the effects of statins on LOEPC growth in vitro. Our findings provide

  8. Canine lymphoma: a review.

    PubMed

    Zandvliet, M

    2016-06-01

    Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20-100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans. Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7-10 months, resulting in a median survival of 10-14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance. This review aims to summarize the relevant data on cL, as well as to provide an update of the recent literature. PMID:26953614

  9. Qi-Shen-Yi-Qi Dripping Pills Promote Angiogenesis of Ischemic Cardiac Microvascular Endothelial Cells by Regulating MicroRNA-223-3p Expression

    PubMed Central

    Dai, Guo-Hua; Liu, Ning; Zhu, Jing-Wei; Yao, Jing; Yang, Chun; Ma, Pei-Ze; Song, Xian-Bo

    2016-01-01

    Traditional Chinese medicine (TCM) research shows that Qi-Shen-Yi-Qi Dripping Pills (QSYQ) can promote ischemic cardiac angiogenesis. Studies have shown that microRNAs (miRNAs) are the key component of gene regulation networks, which play a vital role in angiogenesis and cardiovascular disease. Mechanisms involving miRNA by which TCM promotes ischemic cardiac angiogenesis have not been reported. We found that microRNA-223-3p (mir-223-3p) was the core miRNA of angiogenesis of rats ischemic cardiac microvascular endothelial cells (CMECs) and inhibited angiogenesis by affecting RPS6KB1/HIF-1α signal pathway in previous study. Based on the results, we observed biological characteristics and optimal dosage for QSYQ intervening in rats ischemic CMECs angiogenesis and concluded that QSYQ low-dose group had the strongest ability to promote angiogenesis of ischemic myocardium. Using miRNA chip and real-time PCR techniques in this study, we identified mir-223-3p as the pivotal miRNA in QSYQ that regulated angiogenesis of ischemic CMECs. From real-time PCR and western blot analysis, research showed that gene and protein expression of factors located RPS6KB1/HIF-1α signaling pathway, including HIF-1α, VEGF, MAPK, PI3K, and AKT, were significantly upregulated by QSYQ to regulate angiogenesis of ischemic CMECs. This study showed that QSYQ promote ischemic cardiac angiogenesis by downregulating mir-223-3p expression in rats ischemic CMECs. PMID:27057198

  10. Activation of Notch-Mediated Protective Signaling in the Myocardium

    PubMed Central

    Gude, Natalie A.; Emmanuel, Gregory; Wu, Weitao; Cottage, Christopher T.; Fischer, Kimberlee; Quijada, Pearl; Muraski, John A.; Alvarez, Roberto; Rubio, Marta; Schaefer, Eric; Sussman, Mark A.

    2013-01-01

    The Notch network regulates multiple cellular processes, including cell fate determination, development, differentiation, proliferation, apoptosis, and regeneration. These processes are regulated via Notch-mediated activity that involves hepatocyte growth factor (HGF)/c-Met receptor and phosphatidylinositol 3-kinase/Akt signaling cascades. The impact of HGF on Notch signaling was assessed following myocardial infarction as well as in cultured cardiomyocytes. Notch1 is activated in border zone cardiomyocytes coincident with nuclear c-Met following infarction. Intramyocardial injection of HGF enhances Notch1 and Akt activation in adult mouse myocardium. Corroborating evidence in cultured cardiomyocytes shows treatment with HGF or insulin increases levels of Notch effector Hes1 in immunoblots, whereas overexpression of activated Notch intracellular domain prompts a 3-fold increase in phosphorylated Akt. Infarcted hearts injected with adenoviral vector expressing Notch intracellular domain treatment exhibit improved hemodynamic function in comparison with control mice after 4 weeks, implicating Notch signaling in a cardioprotective role following cardiac injury. These results indicate Notch activation in cardiomyocytes is mediated through c-Met and Akt survival signaling pathways, and Notch1 signaling in turn enhances Akt activity. This mutually supportive crosstalk suggests a positive survival feedback mechanism between Notch and Akt signaling in adult myocardium following injury. PMID:18369158

  11. Lipofuscin accumulation in ageing myocardium & its removal by meclophenoxate.

    PubMed

    Patro, N; Sharma, S P; Patro, I K

    1992-06-01

    A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown thus that deposition of the age-pigment, lipofuscin, can be accepted as an index of cellular ageing. PMID:1512044

  12. Ultrastructural morphometry of the myocardium of Thunnus alalunga.

    PubMed

    Breisch, E A; White, F; Jones, H M; Laurs, R M

    1983-01-01

    The common ventricle in the heart of the Thunnus alalunga was studied. The ventricular myocardium consists of an outer compact layer and a thick inner spongy layer. The compact layer has slightly larger cells (4-6 microns diameter) than the spongy layer (2.5-5 microns diameter). Ultrastructurally the myocardium displays normal arrangements of myofibrils and mitochondria. The sarcoplasmic reticulum is poorly developed. The intercalated discs are simple with the fascia adherens being the most frequent junctional type observed; occasionally a desmosome was seen. Nexus type junctions are present but are unassociated with the intercalated discs. There are no t-tubules evident but the plasmalemma exhibits numerous caveolae which rarely form couplings with the sarcoplasmic reticulum. A morphometric analysis of the volume percent of mitochondria and myofibrils showed that the myocardial cells in the spongy layer of the heart have a significantly greater volume percentage of mitochondria than the compact layer. No significant differences were found between myocardial regions when the volume percentages of myofibrils were compared. The physiological studies revealed that the albacore tuna has heart rates (120 bpm) and ventricular blood pressures (100 mmHg) that are among the highest reported for fish. PMID:6616575

  13. What's eating you? Canine scabies.

    PubMed

    Burroughs, Richard F; Elston, Dirk M

    2003-08-01

    Infestation with Sarcoptes scabiei var canis, the causative strain of canine scabies, can produce a pruritic rash in humans. The rash generally manifests within 24 to 96 hours of contact with the affected pet. Scrapings are generally negative, and the correct diagnosis requires a high index of suspicion. PMID:12953932

  14. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  15. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    PubMed Central

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  16. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection

    PubMed Central

    Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. PMID:27413751

  17. MicroRNA Dysregulation in Diabetic Ischemic Heart Failure Patients

    PubMed Central

    Greco, Simona; Fasanaro, Pasquale; Castelvecchio, Serenella; D’Alessandra, Yuri; Arcelli, Diego; Di Donato, Marisa; Malavazos, Alexis; Capogrossi, Maurizio C.; Menicanti, Lorenzo; Martelli, Fabio

    2012-01-01

    Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non–end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients. PMID:22427379

  18. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... dilution in a varying serum-constant virus neutralization test using 50 to 300 TCID50 of canine adenovirus... virus neutralization test using 50 to 300 TCID50 of canine adenovirus. (i) A geometric mean titer of...

  19. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... dilution in a varying serum-constant virus neutralization test using 50 to 300 TCID50 of canine adenovirus... virus neutralization test using 50 to 300 TCID50 of canine adenovirus. (i) A geometric mean titer of...

  20. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... dilution in a varying serum-constant virus neutralization test using 50 to 300 TCID50 of canine adenovirus... virus neutralization test using 50 to 300 TCID50 of canine adenovirus. (i) A geometric mean titer of...

  1. Probability mapping of scarred myocardium using texture and intensity features in CMR images

    PubMed Central

    2013-01-01

    Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

  2. Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction?

    PubMed

    Berger, Marc Moritz; Macholz, Franziska; Mairbäurl, Heimo; Bärtsch, Peter

    2015-11-15

    Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed. PMID:26089545

  3. Microglia in ischemic brain injury

    PubMed Central

    Weinstein, Jonathan R; Koerner, Ines P; Möller, Thomas

    2010-01-01

    Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity. PMID:20401171

  4. Genetics of Human and Canine Dilated Cardiomyopathy

    PubMed Central

    Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F. N.; Cobb, Malcolm; Mongan, Nigel P.; Rutland, Catrin S.

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed. PMID:26266250

  5. Activated Protein C Protects Myocardium Via Activation of Anti-apoptotic Pathways of Survival in Ischemia-reperfused Rat Heart

    PubMed Central

    Ding, Jia-Wang; Yang, Jun; Liu, Zhao-Qi; Zhang, Yan; Yang, Jian; Li, Song; Li, Li

    2010-01-01

    Activated protein C (APC) is known to be beneficial on ischemia reperfusion injury in myocardium. However, the protection mechanism of APC is not fully understood. The purpose of this study was to investigate the effects and possible mechanisms of APC on myocardial ischemic damage. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 hr of reperfusion. Rats were randomly divided into four groups; Sham, I/R, APC preconditioning and postconditioning group. Myocardial infarct size, apoptosis index, the phosphorylation of ERK1/2, Bcl-2, Bax and cytochrome c genes and proteins were assessed. In APC-administrated rat hearts, regardless of the timing of administration, infarct size was consistently reduced compared to ischemia/reperfusion (I/R) rats. APC improved the expression of ERK1/2 and anti-apoptotic protein Bcl-2 which were significantly reduced in the I/R rats. APC reduced the expression of pro-apoptotic genes, Bax and cytochrome c. These findings suggest that APC produces cardioprotective effect by preserving the expression of proteins and genes involved in anti-apoptotic pathways, regardless of the timing of administration. PMID:21060750

  6. Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina

    SciTech Connect

    Camici, P.; Araujo, L.I.; Spinks, T.; Lammertsma, A.A.; Kaski, J.C.; Shea, M.J.; Selwyn, A.P.; Jones, T.; Maseri, A.

    1986-07-01

    Regional myocardial perfusion and exogenous glucose uptake were assessed with rubidium-82 (82Rb) and 18F-2-fluoro-2-deoxyglucose (FDG) in 10 normal volunteers and 12 patients with coronary artery disease and stable angina pectoris by means of positron emission tomography. In patients at rest, the myocardial uptake of /sup 82/Rb and FDG did not differ significantly from that measured in normal subjects. The exercise test performed within the positron camera in eight patients produced typical chest pain and ischemic electrocardiographic changes in all. In each of the eight patients a region of reduced cation uptake was demonstrated in the /sup 82/Rb scan recorded at peak exercise, after which uptake of /sup 82/Rb returned to the control value 5 to 14 min after the end of the exercise. In these patients, FDG was injected in the recovery phase when all the variables that were altered during exercise, including regional myocardial /sup 82/Rb uptake, had returned to control values. In all but one patient, FDG accumulation in the regions of reduced /sup 82/Rb uptake during exercise was significantly higher than that in the nonischemic regions, i.e., the ones with a normal increment of /sup 82/Rb uptake on exercise. In the nonischemic areas, FDG uptake was not significantly different from that found in normal subjects after exercise. In conclusion, myocardial glucose transport and phosphorylation seem to be enhanced in the postischemic myocardium of patients with exercise-induced ischemia.

  7. High b value DWI in evaluation of the hyperacute cerebral ischemia at 3T: A comparative study in an embolic canine stroke model

    PubMed Central

    Cheng, Qiguang; Xu, Xiaoquan; Zu, Qingquan; Lu, Shanshan; Yu, Jing; Liu, Xinglong; Wang, Bin; Shi, Haibin; Teng, Gaojun; Liu, Sheng

    2016-01-01

    Previous studies have indicated that the temporal change of relative diffusion weighted imaging (rDWI) signal intensity may help to determine the onset time of a stroke. Furthermore, several studies have indicated that high b value DWI offered improved detection rates for hyper-acute ischemic lesions compared with standard b value DWI. However, the temporal changes of the rDWI on high b value DWI remain unclear. Therefore, based on our embolic canine stroke model, we evaluated the temporal evolution of rDWI on high b value DWI, and further compared its diagnostic value in predicting the onset time of ischemic stroke with rDWI on standard b value DWI. Twelve canine MCAO models were established, and DWI was performed at 1, 2, 3, 4, 5 and 6 h after MCAO, with 3 b values of 1,000, 2,000 and 3,000. High b value DWI detected all ischemic lesions after 1 h, while standard b value did not detect the ischemic lesions in one dog at 1 h. With all three of the tested b values, rDWIs increased continuously within 6 h, while relative apparent diffusion coefficient (rADC) values rapidly decreased in 1 h, then became relatively stable. The area under the curve values for rDWI with b value of 1,000, 2,000 and 3,000, in predicting ischemic lesions within 3 h were 0.897, 0.929 and 0.938, while for rADC were 0.645, 0.583 and 0.599, respectively. Therefore, the results indicated that the rDWI was helpful in aging hyper-acute ischemic stroke, while rADC appeared not to be. High b value DWI had a higher detection rate for ischemic lesions and better predictive efficacy in determining the onset time of hyper-acute stroke. PMID:27446301

  8. Applications of laser in ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Chen, Mingzhe; Zhang, Yongzhen

    1999-09-01

    Current data demonstrate that laser coronary angioplasty is most useful in complex lesions not well suited for percutaneous transluminal coronary angioplasty (PTCA). It is not `stand-alone' procedure, and should be considered an adjunct to PTCA or stenting. To date, there are not data supporting reduction of restenosis. Direct myocardial revascularization (DMR), either transmyocardial revascularization (TMR) or percutaneous (catheter-based) myocardial revascularization (PMR), uses laser to create channels between ischemic myocardium and left ventricular cavity. Candidates include patients with chronic, severe, refractory angina and those unable to undergo angioplasty or bypass surgery because conduits or acceptable target vessels are lacking. Although the mechanisms of action of DMR have not yet been clearly elucidated, but several theories have been proposed, including channel patency, angiogenesis, and denervation. TMR, typically requiring open thoracotomy, is effective for improving myocardial perfusion and reducing angina. Pilot studies demonstrate that clinical application of PMR is feasible and safe and effective for decreasing angina. Late sequelae also remain to be determined. An ongoing randomized clinical trial is comparing PMR with conventional medical therapy in patients with severe, refractory angina and disease unamenable to angioplasty or bypass surgery.

  9. Lasers in the treatment of ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Zhang, Yongzhen; Chen, Mingzhe

    2000-10-01

    Myocardial revascularization by laser is a new treatment modality for chronic, severe, refractory angina in the patients with coronary heart disease that is not amenable to angioplasty (PTCA) or bypass surgery (CABG). Transmyocardial revascularization (TMR), typically requiring open thoracotomy, uses laser to create channels that would directly carry blood from left ventricular cavity into the ischemic myocardium. Current data indicate that TMR may provide these patients with improvement in angina severity, quality of life, and myocardial perfusion. The greatest potential future use of TMR is as an adjunct to CABG in patients with disease that prevents bypass grafting due to lack of distal targets or a conduit. Recently, as percutaneous (catheter-based) myocardial revascularization (PMR) has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle. The early results with PMR seem encouraging. Randomized clinical trial has demonstrated symptomatic improvement and increased exercise capacity. The risk: benefit ratio for PMR appears to be much more favorable than that for TMR. The mechanisms of action of them have not yet been clearly elucidated, and several theories have been proposed, including channel patency, angiogenesis, denervation, and placebo effect. The challenge of TMR/PMR is related to improvement of perioperative outcomes and long-term survival without worsening of left ventricular function. In future, it may be feasible to combine TMR/PMR with intramyocardial delivery of angiogenic growth factors to induce further new blood vessel formation.

  10. Growth differentiation factor 15 may protect the myocardium from no-reflow by inhibiting the inflammatory-like response that predominantly involves neutrophil infiltration

    PubMed Central

    ZHANG, MEI; PAN, KUNYING; LIU, QIANPING; ZHOU, XIN; JIANG, TIEMIN; LI, YUMING

    2016-01-01

    The aim of the current study was to investigate the time course of the expression of growth differentiation factor-15 (GDF-15) in rat ischemic myocardium with increasing durations of reperfusion, and to elucidate its physiopathological role in the no-reflow phenomenon. Wistar rats were randomly divided into ischemia reperfusion (I/R) and sham groups, and myocardial I/R was established by ligation of the left anterior descending coronary artery for 1 h followed by reperfusion for 2, 4, 6, 12, 24 h and 7 days whilst rats in the sham group were subjected to a sham operation. The expression levels of GDF-15 and ICAM-1 were measured, in addition to myeloperoxidase (MPO) activity. The myocardial anatomical no-reflow and infarction areas were assessed. The area at risk was not significantly different following various periods of reperfusion, while the infarct area and no-reflow area were significantly greater following 6 h of reperfusion (P<0.05). The mRNA and protein expression levels of GDF-15 were increased during the onset and development of no-reflow, and peaked following 24 h of reperfusion. MPO activity was reduced with increasing reperfusion duration, while ICAM-1 levels were increased. Hematoxylin and eosin staining demonstrated that myocardial neutrophil infiltration was significantly increased by I/R injury, in particular following 2, 4 and 6 h of reperfusion. GDF-15 expression levels were negatively correlated with MPO activity (r=−0.55, P<0.001), and the MPO activity was negatively correlated with the area of no-reflow (r=−0.46, P<0.01). By contrast, GDF-15 was significantly positively correlated with ICAM-1 levels (r=0.52, P<0.01), which additionally were demonstrated to be significantly positively associated with the size of the no-reflow area (r= 0.39, P<0.05). The current study demonstrated the time course effect of reperfusion on the expression of GDF-15 in the myocardial I/R rat model, with the shorter reperfusion times (6 h) resulting in

  11. Developmental Changes in Expression and Biophysics of Ion Channels in the Canine Ventricle

    PubMed Central

    Cordeiro, Jonathan M; Panama, Brian K; Goodrow, Robert; Zygmunt, Andrew C; White, Casey; Treat, Jacqueline A; Zeina, Tanya; Nesterenko, Vladislav V; Di Diego, José M; Burashnikov, Alexander; Antzelevitch, Charles

    2013-01-01

    Background Developmental changes in the electrical characteristics of the ventricular myocardium are not well defined. This study examines the contribution of inwardly rectifying K+ current (IK1), transient outward K+ current (Ito), delayed rectifier K+ currents (IKr and IKs) and sodium channel current (INa) to repolarization in the canine neonate myocardium. Methods Single myocytes isolated from the left ventricle of 2-3 week old canine neonate hearts were studied using patch-clamp techniques. Results Neonate cells were ~6-fold smaller than those of adults (28.8±8.8 vs. 176±6.7 pF). IK1 was larger in neonate myocytes and displayed a substantial inward component and an outward component with negative slope conductance, peaking at −60 mV (4.13 pA/pF). IKr tail currents (at −40 mV), were small (<20 pA). IKs could not be detected, even after exposure to isoproterenol (100 nM). Ito was also absent in the neonate, consistent with the absence of a phase 1 in the action potential. Peak INa, late INa and ICa were smaller in the neonate compared with adult. KCND3, KCNIP2 and KCNQ1 mRNA expression was half, while KCNH2 was equal and KCNJ2 was greater in the neonate when compared with adults. Conclusions Two major repolarizing K+ currents (IKs and Ito) present in adult ventricular cells are absent in the 2 week old neonate. Peak and late INa are significantly smaller in the neonate. Our results suggest that the absence of these two currents in the neonate heart may increase the susceptibility to arrhythmias under certain long QT conditions. PMID:24035801

  12. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.

    PubMed

    Miyahara, Yoshinori; Nagaya, Noritoshi; Kataoka, Masaharu; Yanagawa, Bobby; Tanaka, Koichi; Hao, Hiroyuki; Ishino, Kozo; Ishida, Hideyuki; Shimizu, Tatsuya; Kangawa, Kenji; Sano, Shunji; Okano, Teruo; Kitamura, Soichiro; Mori, Hidezo

    2006-04-01

    Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration. PMID:16582917

  13. Cardiac magnetic resonance T1 mapping of left atrial myocardium

    PubMed Central

    Beinart, Roy; Khurram, Irfan M.; Liu, Songtao; Yarmohammadi, Hirad; Halperin, Henry R.; Bluemke, David A.; Gai, Neville; van der Geest, Rob J.; Lima, Joao A.C.; Calkins, Hugh; Zimmerman, Stefan L.; Nazarian, Saman

    2013-01-01

    BACKGROUND Cardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis. OBJECTIVES To (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures. METHODS CMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements. RESULTS The median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364–428] ms) compared to healthy volunteers (459 [interquartile range 418–532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model, adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025). CONCLUSIONS Measurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues. PMID:23643513

  14. Quantification of fiber orientation in the canine atrial pacemaker complex using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ambrosi, Christina M.; Fedorov, Vadim V.; Schuessler, Richard B.; Rollins, Andrew M.; Efimov, Igor R.

    2012-07-01

    The atrial pacemaker complex is responsible for the initiation and early propagation of cardiac impulses. Optical coherence tomography (OCT), a nondestructive imaging modality with spatial resolutions of ˜1 to 15 μm, can be used to identify unique fiber orientation patterns in this region of the heart. Functionally characterized canine sinoatrial nodes (SAN) (n=7) were imaged using OCT up to ˜1 mm below the endocardial tissue surface. OCT images were directly compared to their corresponding histological sections. Fiber orientation patterns unique to the crista terminalis (CT), SAN, and surrounding atrial myocardium were identified with dominant average fiber angles of 89±12 deg, 110±16 deg, and 95±35 deg, respectively. Both the CT and surrounding atrial myocardium displayed predominantly unidirectionally based fiber orientation patterns within each specimen, whereas the SAN displayed an increased amount of fiber disarray manifested quantitatively as a significantly greater standard deviation in fiber angle distribution within specimens [33±7 deg versus 23±5 deg, atrium (p=0.02); 18±3 deg, CT (p=0.0003)]. We also identified unique, local patterns of fiber orientation specific to the functionally characterized block zone. We demonstrate the ability of OCT in detecting components of the atrial pacemaker complex which are intimately involved in both normal and abnormal cardiac conduction.

  15. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  16. Canine adenovirus based rabies vaccines.

    PubMed

    Tordo, N; Foumier, A; Jallet, C; Szelechowski, M; Klonjkowski, B; Eloit, M

    2008-01-01

    Adenovirus based vectors are very attractive candidates for vaccination purposes as they induce in mammalian hosts potent humoral, mucosal and cellular immune responses to antigens encoded by the inserted genes. We have generated E1-deleted and replication-competent recombinant canine type-2 adenoviruses expressing the rabies virus glycoprotein (G). The effectiveness of both vectors to express a native G protein has been characterized in vitro in permissive cell lines. We compared the humoral and cellular immune responses induced in mice by intramuscular injection of the recombinant canine adenovirus vectors with those induced by a human (Ad5) E1-deleted virus expressing the same rabies G protein. Humoral responses specific to the adenoviruses or the rabies glycoprotein antigens were studied. The influence of the mouse strain was observed using replication-competent canine adenovirus. A high level of rabies neutralizing antibody was observed upon i.m. inoculation, and 100% of mice survived lethal challenge. These results are very promising in the perspective of oral vaccine for dog rabies control. PMID:18634509

  17. Genome Sequence of Canine Herpesvirus

    PubMed Central

    Papageorgiou, Konstantinos V.; Suárez, Nicolás M.; Wilkie, Gavin S.; McDonald, Michael; Graham, Elizabeth M.; Davison, Andrew J.

    2016-01-01

    Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the genome sequences of three viral strains (0194, V777 and V1154) isolated in the United Kingdom between 1985 and 2000. The sequences are very closely related to each other. The canine herpesvirus genome is estimated to be 125 kbp in size and consists of a unique long sequence (97.5 kbp) and a unique short sequence (7.7 kbp) that are each flanked by terminal and internal inverted repeats (38 bp and 10.0 kbp, respectively). The overall nucleotide composition is 31.6% G+C, which is the lowest among the completely sequenced alphaherpesviruses. The genome contains 76 open reading frames predicted to encode functional proteins, all of which have counterparts in other alphaherpesviruses. The availability of the sequences will facilitate future research on the diagnosis and treatment of canine herpesvirus-associated disease. PMID:27213534

  18. Canine leishmaniosis - an emerging disease.

    PubMed

    Kaszak, Ilona; Planellas, Marta; Dworecka-Kaszak, Bożena

    2015-01-01

    Canine leishmaniosis (CanL) is an invasive disease of dogs, caused by Leishmania spp. parasites transmitted by the bite of an infected phlebotomine sand fly. CanL is declared an important disease by World Organisation for Animal Health (OIE). Due to its zoonotic potential is of a great importance the prevention of this disease in non endemic areas. Canine leishmaniosis is endemic disease in more than 70 countries and is a common disease in Mediterranean region. Recently, many cases have been reported in non endemic areas, like United Kingdom, Germany and Poland as well, where this disease is considered exotic. The aim of this article is to summarize shortly canine leishmaniosis, it's transmission, clinical manifestations, diagnostics procedure, treatment, prognosis and prevention. Increasing knowledge about this disease can be of a great use for veterinary surgeons from countries where CanL is an emerging disease. Multiple clinical presentations of CanL should aware clinicians to include leishmaniosis in the differential diagnosis of most clinical cases. Unfortunately, even if dogs recover clinically after treatment, complete elimination of Leishmania spp. is rarely achieved, and they remain infected and may relapse. PMID:26342500

  19. Magnetic resonance imaging and multi-detector computed tomography assessment of extracellular compartment in ischemic and non-ischemic myocardial pathologies

    PubMed Central

    Saeed, Maythem; Hetts, Steven W; Jablonowski, Robert; Wilson, Mark W

    2014-01-01

    Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume (ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular (approximately 10% of tissue volume), interstitium (approximately 15%) and intracellular (approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types I/III collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis (e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy (hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging (MRI) has the ability to characterize tissue proton relaxation times (T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI (DE-MRI) and multi-detector computed tomography (DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary

  20. The alteration of interelemental ratios in myocardium under the congenital heart disease (SRXRF)

    NASA Astrophysics Data System (ADS)

    Trunova, V. A.; Zvereva, V. V.; Okuneva, G. N.; Levicheva, E. N.

    2007-05-01

    It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower.

  1. Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness.

    PubMed

    Pan, Jingrui; Li, Xiangpen; Peng, Ying

    2016-07-01

    Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future. PMID:26812782

  2. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium. PMID:23598869

  3. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  4. Are neonatal stem cells as effective as adult stem cells in providing ischemic protection?

    PubMed Central

    Markel, Troy A.; Crisostomo, Paul R.; Manukyan, Maiuxi C.; Al-Azzawi, Dalia; Herring, Christine M.; Lahm, Tim; Novotny, Nathan M.; Meldrum, Daniel R.

    2009-01-01

    Background Bone marrow stem cells (BMSCs) may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. However, stem cells from older hosts exhibit decreased function during stress. We therefore hypothesized that: 1) BMSCs derived from neonatal hosts would provide protection to ischemic myocardium; and 2) neonatal stem cells would enhance post-ischemic myocardial recovery above that seen with adult stem cell therapy. Materials and Methods Female adult Sprague-Dawley rat hearts were subjected to an ischemia/reperfusion protocol via Langendorff isolated heart preparation (15 minutes equilibration, 25 minutes ischemia, and 60 minutes reperfusion). BMSCs were harvested from adult and neonatal mice and cultured through several passages under normal conditions (37 C, 5% CO2/air). Immediately prior to ischemia, one million adult or neonatal BMSCs were infused into the coronary circulation. Cardiac functional parameters were continuously recorded. Results Pretreatment with adult BMSCs significantly increased post-ischemic myocardial recovery as noted by improved left ventricular developed pressure, end diastolic pressure, contractility, and rate of relaxation. Neonatal stem cells, however, did not cause any noticeable improvement in myocardial functional parameters following ischemia. Conclusion Neonatal and adult BMSCs are distinctly different in the degree of beneficial tissue protection that they can provide. The data herein suggests that a critical age exists as to when stem cells become fully activated to provide their beneficial protective properties. Defining the genes that initiate these protective properties may allow for genetic amplification of beneficial signals, and the generation of “super stem cells” that provide maximum protection to ischemic tissues. PMID:18805555

  5. Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.

    PubMed

    Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

    2004-04-01

    Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, P<0.01). The reduction of interstitial fibrosis is accompanied by an increase in myocardial hHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury. PMID:14981066

  6. Roles of Chinese herbal medicines in ischemic heart diseases (IHD) by regulating oxidative stress.

    PubMed

    Wang, Dawei; Wang, Jin; Liu, Yuntao; Zhao, Zhen; Liu, Qing

    2016-10-01

    Ischemic heart disease (IHD) basing on atherosclerosis (AS) is known as a top killer for decades. Oxidative stress, representing excessive oxidation and insufficient elimination, has been proved to be a critical molecular mechanism of IHD and accompanying myocardium dysfunction. Therefore, anti-oxidation therapy may be efficient. Chinese herbal medicine, including extractive compounds, decoctions, patent drugs, and injections, has shown its enormous potential in prevention and treatment of IHD as an effective antioxidant in experimental studies. The aim of this review is to highlight recent studies of Chinese herbal medicine in regulating oxidative stress in IHD. These studies represent recent progress of IHD treatment and indicate the possible pathways and target spots of Chinese herbal medicine. PMID:27390948

  7. [Ischemic cerebrovascular accidents in childhood].

    PubMed

    Pascual Pascual, S I; Pascual Castroviejo, I; Vélez, A

    1988-04-01

    Authors review 53 children, aged 0 to 14 years, affected with cerebrovascular ischemic strokes. Largest aetiological groups were: a) congenital heart disease, 16 patients; b) arteritis of unknown cause, 11; c) idiopathic arterial occlusion without arteritis images on angiography, 7; d) moyamoya disease, 6; and d) local or systemic infections, 5. The mode of onset was as completed stroke in 72% and stroke in evolution in 24%. After acute stage 17.6% of patients presented other definitive strokes, 11.7% suffered only transient ischemic strokes (TIA), and 4% reversible ischemic neurologic deficits (RIND). Mean follow-up was 4.36 years, 9.8% of patients died, 11.8% recovered completely and 52.9% improved after initial stroke. Poor global evolution was associated with heart disease (p less than 0.05) and with onset of strokes before age 2 (p less than 0.05). Most important sequelae, besides motor impairment, were epilepsy (49%) and mental retardation (50% got less than IQ 80). Late epilepsy was associated with seizures at onset (p less than 0.05). Clinical factors of adverse mental development were: a) seizures at onset, b) late epilepsy and c) stroke before age 2. 66% of cases had two or more arterial lesions in the same or in different arterial trees. Therefore, embolic and arteritic factors probably play an important role in infancy and childhood stroke. PMID:3400936

  8. Intravenous thrombolytics for ischemic stroke.

    PubMed

    Barreto, Andrew D

    2011-07-01

    For many decades, intravenous (IV) thrombolytics have been delivered to treat acute thrombosis. Although these medications were originally effective for coronary thrombosis, their mechanisms have proven beneficial for many other disease processes, including ischemic stroke. Treatment paradigms for acute ischemic stroke have largely followed those of cardiology. Specifically, the aim has been to recanalize the occluded artery and to restore perfusion to the brain that remains salvageable. To that end, rapid clot lysis was sought using thrombolytic medicines already proven effective in the coronary arteries. IV-thrombolysis for ischemic stroke began its widespread adoption in the late 1990s after the publication of the National Institute of Neurological Disorders and Stroke study. Since that time, other promising IV-thrombolytics have been developed and tested in human trials, but as of yet, none have been proven better than a placebo. Adjunctive treatments are also being evaluated. The challenge remains balancing reperfusion and salvaging brain tissue with the potential risks of brain hemorrhage. PMID:21638138

  9. Bilateral Mandibular Supernumerary Canines: A Case Report

    PubMed Central

    Abouei Mehrizi, Ehsan; Semyari, Hassan; Eslami Amirabadi, Gholamreza

    2010-01-01

    Supernumerary teeth are defined as the teeth developed in excess of the number found in a normal dentition. Supernumerary canine is an extremely rare finding particularly in the mandible. This case report presents a 25-year-old female patient with the unique feature of bilateral mandibular supplemental supernumerary canines. The patient was non-syndromic without any other supernumerary teeth. PMID:23346342

  10. Canine and feline parasitic zoonoses in China

    PubMed Central

    2012-01-01

    Canine and feline parasitic zoonoses have not been given high priority in China, although the role of companion animals as reservoirs for zoonotic parasitic diseases has been recognized worldwide. With an increasing number of dogs and cats under unregulated conditions in China, the canine and feline parasitic zoonoses are showing a trend towards being gradually uncontrolled. Currently, canine and feline parasitic zoonoses threaten human health, and cause death and serious diseases in China. This article comprehensively reviews the current status of major canine and feline parasitic zoonoses in mainland China, discusses the risks dogs and cats pose with regard to zoonotic transmission of canine and feline parasites, and proposes control strategies and measures. PMID:22839365

  11. Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs.

    PubMed Central

    Sassen, L. M.; den Boer, M. O.; Rensen, R. J.; Saxena, P. R.; Verdouw, P. D.

    1988-01-01

    1. The ability of the cardioselective beta-adrenoceptor antagonist bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropyl-amino -2-propanol hemifumarate, EMD 33512) to suppress isoprenaline-induced increases in heart rate and maximal rate of rise in left ventricular pressure (LVdP/dtmax) was studied in 6 anaesthetized pigs given 4 cumulative doses (16, 64, 256 and 1024 micrograms kg-1). Bisoprolol was about 2 times more effective in suppressing isoprenaline-induced increases in LVdP/dtmax than those in heart rate. 2. In 8 animals which had a partial stenosis of the left anterior descending coronary artery (LADCA), the effects of 3 consecutive doses (50, 200 and 750 micrograms kg-1) of bisoprolol were studied on systemic haemodynamics, regional myocardial perfusion and function. The effects of the drug were compared with those obtained in a group of 9 animals with LADCA stenosis which did not receive any treatment. 3. The lowest dose of bisoprolol (50 micrograms kg-1) increased perfusion of the ischaemic myocardium (which had been reduced from 123 +/- 20 ml min-1 100 g-1 to 42 +/- 11 ml min-1 100 g-1) by 21 +/- 10 ml min-1 100 g-1 (P less than 0.05). In particular the subendocardial layers, which were most severely affected by the stenosis (a decrease from 128 +/- 19 ml min-1 100 g-1 to 20 +/- 6 ml min-1 100 g-1) benefited from the administration of the drug (an increase of 30 +/- 10 ml min-1 100 g-1). Perfusion of the subepicardium was not significantly affected. With the higher dose only a minor additional improvement in perfusion of the ischaemic myocardium was observed. 4. The negative chronotropic response is the most likely factor leading to the improvement in perfusion. 5. Myocardial wall thickening, which decreased from 41 +/- 2% to 9 +/- 4% (P less than 0.05) due to the hypoperfusion, did not improve after administration of the drug. This lack of improvement may possibly be due to the duration of ischaemia before and the magnitude of the

  12. Probing myocardium biomechanics using quantitative optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

    2015-03-01

    We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young's modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

  13. [Dynamics of lesions to the myocardium in experimental hyper- cholesterolemia].

    PubMed

    Rózycka, Z; Lewicki, Z; Wutzen, J

    1989-04-10

    Dynamics of changes in the myocardium of rabbits subjected to food hypercholesterolemia lasting from 6 to 16 weeks was investigated. An intensification of coronary atheromatosis was proportional to the duration of the high-cholesterol diet. There were observed focal and growing in time damages of cardiomyocytes. They were sharply outlined in atherosclerotically changed coronary arteries. The following morphological and histochemical changes have been observed: increased acidophilia and fuchsinophilia in the single and grouped muscle fibres, foci of infiltrations by mononuclear cells, contraction bands, and outlines of myocardial fibres, separation of myofibrils, granular disintegration of cardiomyocytes, healed infarcts, depletion and excessive accumulation of glycogen in muscle fibres, presence of neutral fats, cholesterol and its esters in atheromatous plaques of coronary arteries, presence of neutral fats in some cardiomyocytes: focal acid phosphates, loss of activity of Mg- and Ca-dependent ATPases and SDH: oedema of mitochondria with disorganization of cristae, disorganisation of fibres and lysis of myofilaments, margination of chromatin in cardiomyocyte nuclei, increased number of lysosomes, intensified symptoms of egzocytosis, widening of channels of sarcoplasmatic reticulum, oedema of endothelium of capillary vessels and increased number of the collagenous fibres in the interstitial space. The results of histological, histochemical and microscopic-electron investigations correlated with each other. It may be considered that the observed damages of cardiomyocytes precede myocardial infarction and result from progressive and increasing ischemia, hypoxia and accumulation of fat substances and cholesterol and its esters in intima of coronary arterioles as well as in cardiomyocytes. PMID:2813156

  14. Microvasculature of the Dog Left Ventricular Myocardium1

    PubMed Central

    Bassingthwaighte, James B.; Yipintsoi, Tada; Harvey, Rodney B.

    2010-01-01

    One of the main branches of the left main coronary artery of normally beating dog hearts was perfused with a silicone elastomer which solidified within the vasculature. Prolonged immersion in increasingly concentrated ethanol and in methyl salicylate rendered the tissue translucent and the vasculature clearly visible. Surfaces were photographed by reflected or transmitted light microscopy, showing large groups of capillaries running parallel to muscle fibers and extending for up to a few centimeters. The arrangement of arteriolar inflows to the capillary network and venular outflows (two to four times as frequent) suggested that functional capillary lengths were 500–1000 μm. Estimates of capillary diameters, presumably at maximal dilatation, were 5.6 ± 1.3 μm. Capillary densities within muscle groups were 3100–3800/mm2, giving intercapillary distances of 19–17.5 μm. With the lesser density value, the capillary surface area is estimated to be 500 cm2/g of myocardium. Inclusion of interfascial spaces lowered the average density to about 2500/mm2. Unbranched capillary lengths averaged 100 μm, with a strongly right-skewed distribution. The anatomic arrangement provides a basis mainly for concurrent flow in neighboring capillaries, and also for some diffusional exchange between inflow and outflow regions. PMID:4596001

  15. Autophagy and mitophagy in the myocardium: therapeutic potential and concerns.

    PubMed

    Jimenez, Rebecca E; Kubli, Dieter A; Gustafsson, Åsa B

    2014-04-01

    The autophagic-lysosomal degradation pathway is critical for cardiac homeostasis, and defects in this pathway are associated with development of cardiomyopathy. Autophagy is responsible for the normal turnover of organelles and long-lived proteins. Autophagy is also rapidly up-regulated in response to stress, where it rapidly clears dysfunctional organelles and cytotoxic protein aggregates in the cell. Autophagy is also important in clearing dysfunctional mitochondria before they can cause harm to the cell. This quality control mechanism is particularly important in cardiac myocytes, which contain a very high volume of mitochondria. The degradation of proteins and organelles also generates free fatty acids and amino acids, which help maintain energy levels in myocytes during stress conditions. Increases in autophagy have been observed in various cardiovascular diseases, but a major question that remains to be answered is whether enhanced autophagy is an adaptive or maladaptive response to stress. This review discusses the regulation and role of autophagy in the myocardium under baseline conditions and in various aetiologies of heart disease. It also discusses whether this pathway represents a new therapeutic target to treat or prevent cardiovascular disease and the concerns associated with modulating autophagy. PMID:24148024

  16. Coagulating activity of the blood, vascular wall, and myocardium under hypodynamia conditions

    NASA Technical Reports Server (NTRS)

    Petrovskiy, B. V. (Editor); Chazov, E. I. (Editor); Andreyev, S. V. (Editor)

    1980-01-01

    In order to study the effects of hypodynamia on the coagulating properties of the blood, vascular wall, and myocardium, chinchilla rabbits were kept for varying periods in special cages which restricted their movements. At the end of the experiment, blood samples were taken and the animals were sacrificed. Preparations were made from the myocardium venae cavae, and layers of the aorta. Two resultant interrelated and mutually conditioned syndromes were discovered: thrombohemorrhagic in the blood and hemorrago-thrombotic in the tissues.

  17. Drinking to near death--acute water intoxication leading to neurogenic stunned myocardium.

    PubMed

    Losonczy, Lia I; Lovallo, Emily; Schnorr, C Daniel; Mantuani, Daniel

    2016-01-01

    Neurogenic stunned myocardium is a rare disease entity that has been typically described as a consequence of subarachnoid hemorrhage and, less commonly, seizures. Here we describe a case of a healthy young woman who drank excessive free water causing acute hyponatremia complicated by cerebral edema and seizure, leading to cardiogenic shock from neurogenic stunned myocardium. Two days later, she had complete return of her normal cardiac function. PMID:26238098

  18. Management of ischemic optic neuropathies

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    Ischemic optic neuropathies (IONs) consist primarily of two types: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

  19. Canine procalcitonin messenger RNA expression.

    PubMed

    Kuzi, Sharon; Aroch, Itamar; Peleg, Keren; Karnieli, Ohad; Klement, Eyal; Dank, Gillian

    2008-09-01

    Procalcitonin is considered an acute phase protein used as both a marker of infection and prognosis in human medicine. Canine procalcitonin has been previously sequenced; however, its use as a diagnostic or prognostic tool in dogs has never been assessed. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay for canine procalcitonin messenger RNA (mRNA) was developed. Whole blood samples were collected from ill and healthy dogs. RNA was extracted and the real-time PCR was assessed. The patients' diagnoses, complete blood cell count, and differential leukocyte count results were recorded. Based on the diagnosis, dogs were divided into 5 groups: inflammatory, infectious, neoplastic, other diseases, and healthy controls. Procalcitonin mRNA expression and the hematological measures were compared between groups, and their correlations were assessed. Procalcitonin mRNA expression was assessed in 70 dogs, including infectious (17), noninfectious inflammatory (17), neoplastic (18), other diseases (7), and healthy controls (11), and was significantly (P < 0.001) higher in all ill dogs versus controls. Procalcitonin may therefore be considered an acutephase protein in dogs. However, there were no significant differences in procalcitonin mRNA expression between ill dog groups and no correlations between its expression levels and hematological measures. In 5 dogs of all disease categories, procalcitonin mRNA expression was measured twice during the course of disease. The changes in its levels were in agreement with the clinical evaluation of improvement or deterioration, suggesting a possible prognostic value. PMID:18776098

  20. Neuroinflammation in advanced canine glaucoma

    PubMed Central

    Jiang, Bing; Harper, Matthew M.; Kecova, Helga; Adamus, Grazyna; Kardon, Randy H.; Grozdanic, Sinisa D.

    2010-01-01

    Purpose The pathophysiological events that occur in advanced glaucoma are not well characterized. The principal purpose of this study is to characterize the gene expression changes that occur in advanced glaucoma. Methods Retinal RNA was obtained from canine eyes with advanced glaucoma as well as from healthy eyes. Global gene expression patterns were determined using oligonucleotide microarrays and confirmed by real-time PCR. The presence of tumor necrosis factor (TNF) and its receptors was evaluated by immunolabeling. Finally, we evaluated the presence of serum autoantibodies directed against retinal epitopes using western blot analyses. Results We identified over 500 genes with statistically significant changes in expression level in the glaucomatous retina. Decreased expression levels were detected for large number of functional groups, including synapse and synaptic transmission, cell adhesion, and calcium metabolism. Many of the molecules with decreased expression levels have been previously shown to be components of retinal ganglion cells. Genes with elevated expression in glaucoma are largely associated with inflammation, such as antigen presentation, protein degradation, and innate immunity. In contrast, expression of many other pro-inflammatory genes, such as interferons or interleukins, was not detected at abnormal levels. Conclusions This study characterizes the molecular events that occur in the canine retina with advanced glaucoma. Our data suggest that in the dog this stage of the disease is accompanied by pronounced retinal neuroinflammation. PMID:21042562

  1. Evidence for canine rehabilitation and physical therapy.

    PubMed

    Millis, Darryl L; Ciuperca, Ionut Alexandru

    2015-01-01

    This article reviews some important studies regarding canine physical rehabilitation. Bones, cartilage, muscles, ligaments, and tendons undergo atrophy if loading is decreased. Knowledge of the changes that occur with immobilization and the time course of events helps in the development of a rehabilitation program to improve tissue integrity. Outcome assessment instruments are clinically useful indicators of patient progress and the success of rehabilitation programs. A number of physical modalities are used in canine rehabilitation, although there are relatively few canine-specific studies. Rehabilitation has specific benefits in the treatment of various orthopedic and neurologic conditions. PMID:25432679

  2. Structure and vascularization of the ventricular myocardium in Holocephali: their evolutionary significance.

    PubMed

    Durán, Ana C; López-Unzu, Miguel A; Rodríguez, Cristina; Fernández, Borja; Lorenzale, Miguel; Linares, Andrea; Salmerón, Francisca; Sans-Coma, Valentín

    2015-06-01

    It was generally assumed that the ventricle of the primitive vertebrate heart was composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal blood. In addition, it was presumed that the mixed ventricular myocardium, consisting of a compacta and a spongiosa, and its supply through coronary arteries appeared several times throughout fish evolution. Recent work has suggested, however, that a fully vascularized, mixed myocardium may be the primitive condition in gnathostomes. The present study of the heart ventricles of four holocephalan species aimed to clarify this controversy. Our observations showed that the ventricular myocardium of Chimaera monstrosa and Harriotta raleighana consists of a very thin compacta overlying a widespread spongiosa. The ventricle of Hydrolagus affinis is composed exclusively of trabeculated myocardium. In these three species there is a well-developed coronary artery system. The main coronary artery trunks run along the outflow tract, giving off subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated by branches of the subepicardial arteries and by penetrating arterial vessels arising directly from the main coronary trunks at the level of the conoventricular junction. The ventricle of Rhinochimaera atlantica has only spongy myocardium supplied by luminal blood. Small coronary arterial vessels are present in the subepicardium, but they do not enter the myocardial trabeculae. The present findings show for the first time that in a wild living vertebrate species, specifically H. affinis, an extensive coronary artery system supplying the whole cardiac ventricle exists in the absence of a well-developed compact ventricular myocardium. This is consistent with the notion derived from experimental work that myocardial cell proliferation and coronary vascular growth rely on distinct developmental programs. Our observations, together with data in the literature on elasmobranchs, support the view that

  3. Comparative functional characterization of canine IgG subclasses.

    PubMed

    Bergeron, Lisa M; McCandless, Erin E; Dunham, Steve; Dunkle, Bill; Zhu, Yaqi; Shelly, John; Lightle, Sandra; Gonzales, Andrea; Bainbridge, Graeme

    2014-01-15

    To date, very little is known about the functional characteristics of the four published canine IgG subclasses. It is not clear how each subclass engages the immune system via complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC), or how long each antibody may last in serum. Such information is critical for understanding canine immunology and for the discovery of canine therapeutic monoclonal antibodies. Through both in vitro and ex vivo experiments to evaluate canine Fc's for effector function, complement binding, FcRn binding, and ADCC, we are now able to categorize canine subclasses by function. The subclasses share functional properties with the four human IgG subclasses and are reported herein with their function-based human analog. Canine Fc fusions, canine chimeras, and caninized antibodies were characterized. Canine subclasses A and D appear effector-function negative while subclasses B and C bind canine Fc gamma receptors and are positive for ADCC. All canine subclasses bind the neonatal Fc receptor except subclass C. By understanding canine IgGs in this way, we can apply what is known of human immunology toward translational and veterinary medicine. Thus, this body of work lays the foundation for evaluating canine IgG subclasses for therapeutic antibody development and builds upon the fundamental scholarship of canine immunology. PMID:24268690

  4. Estimating canine tooth crown height in early Australopithecus.

    PubMed

    Plavcan, J Michael; Ward, Carol V; Paulus, Faydre L

    2009-07-01

    Canine tooth size reduction and the associated reduction in canine dimorphism is a basal hominin character that also provides important evidence for models of behavioral evolution. Two specimens of Australopithecus anamensis (KNM-KP 29287 and KNM-KP 29283) that do not preserve the canine crown, but do preserve the root or alveolus, appear to suggest that canine size variation and canine dimorphism in this species may have been greater than in other hominins. We evaluate canine root and crown dimensions in a series of extant hominoids, and estimate canine crown height in Australopithecus afarensis and A. anamensis. Our results demonstrate that it is possible to generate estimates of canine crown height from basal canine crown and root dimensions with a moderate degree of accuracy. Estimates of maxillary canine crown size for A. anamensis are slightly larger than those of A. afarensis, and are approximately the same size as canines of modern female chimpanzees. Estimated mandibular canine crown height is very similar in the two species. Variation within the A. anamensis sample of estimated canine crown heights is similar to that of modern humans, suggesting a low degree of sexual dimorphism. Inclusion of estimates for KNM-KP 29287 and KNM-KP 29283 does not substantially increase either the estimate of overall canine size or variation for A. anamensis. PMID:19482334

  5. Peroxisomal Biogenesis in Ischemic Brain

    PubMed Central

    Young, Jennifer M.; Nelson, Jonathan W.; Cheng, Jian; Zhang, Wenri; Mader, Sarah; Davis, Catherine M.; Morrison, Richard S.

    2015-01-01

    Abstract Aims: Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia. Results: Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD. Innovation: This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy. Conclusion: Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons. Antioxid. Redox Signal. 22, 109–120. PMID:25226217

  6. Symptoms of transient ischemic attack.

    PubMed

    Kim, Jong S

    2014-01-01

    Transient ischemic attack (TIA) is a cerebrovascular disease with temporary (<24 h) neurological symptoms. The symptoms of TIA patients are largely similar to those of ischemic stroke patients and include unilateral limb weakness, speech disturbances, sensory symptoms, visual disturbances, and gait difficulties. As these symptoms are transient, they are frequently evaluated based on patients' subjective reports, which are less precise than those of patients with stroke whose longer-lasting symptoms and signs can be reliably assessed by physicians. Some symptoms, such as monocular blindness, are much more common in TIA than in stroke, and limb shaking occurs almost exclusively in TIA patients. On the other hand, symptoms like hemivisual field defects or limb ataxia are underappreciated in TIA patients. These transient neurological symptoms are not necessarily caused by cerebrovascular diseases, but can be produced by a variety of non-vascular diseases. Careful history taking, examination, and appropriate imaging tests are needed to differentiate these TIA mimics from TIA. Each TIA symptom has a different specificity and sensitivity, and there has been an effort to assess the outcome of the patients through the use of specific clinical features. On top of this, recent developments in imaging techniques have greatly enhanced our ability to predict the outcomes of TIA patients. Perception or recognition of TIA symptoms may differ according to the race, sex, education, and specialty of physicians. Appropriate education of both the general population and physicians with regard to TIA symptoms is important as TIAs need emergent evaluation and treatment. PMID:24157558

  7. Etiology of maxillary canine impaction: a review.

    PubMed

    Becker, Adrian; Chaushu, Stella

    2015-10-01

    This article is a review that enumerates the causes of impaction of the maxillary permanent canines, including hard tissue obstructions, soft tissue lesions, and anomalies of neighboring teeth, and discusses the much-argued relationship between environmental and genetic factors. These phenomena have been shown in many investigations to accompany the diagnosis of canine impaction and have been presented as unrelated anomalous features, each of which is etiologically construed as genetic, including the aberrant canine itself. While in general the influence of genetics pervades the wider picture, a guidance theory proposes an alternative etiologic line of reasoning and interpretation of these studies, in which the same genetically determined anomalous features provide an abnormal milieu in which the canine is reared and from which it is guided in its misdirected and often abortive path of eruption. PMID:26432311

  8. Blueberry-Enriched Diet Protects Rat Heart from Ischemic Damage

    PubMed Central

    Ahmet, Ismayil; Spangler, Edward; Shukitt-Hale, Barbara; Juhaszova, Magdalena; Sollott, Steven J.; Joseph, James A.; Ingram, Donald K.; Talan, Mark

    2009-01-01

    Objectives to assess the cardioprotective properties of a blueberry enriched diet (BD). Background Reactive oxygen species (ROS) play a major role in ischemia-related myocardial injury. The attempts to use synthetic antioxidants to block the detrimental effects of ROS have produced mixed or negative results precipitating the interest in natural products. Blueberries are readily available product with the highest antioxidant capacity among fruits and vegetables. Methods and Results Following 3-mo of BD or a regular control diet (CD), the threshold for mitochondrial permeability transition (tMPT) was measured in isolated cardiomyocytes obtained from young male Fischer-344 rats. Compared to CD, BD resulted in a 24% increase (p<0.001) of ROS indexed tMPT. The remaining animals were subjected to a permanent ligation of the left descending coronary artery. 24 hrs later resulting myocardial infarction (MI) in rats on BD was 22% less than in CD rats (p<0.01). Significantly less TUNEL(+) cardiomyocytes (2% vs 9%) and 40% less inflammation cells were observed in the myocardial area at risk of BD compared to CD rats (p<0.01). In the subgroup of rats, after coronary ligation the original diet was either continued or switched to the opposite one, and cardiac remodeling and MI expansion were followed by serial echocardiography for 10 weeks. Measurements suggested that continuation of BD or its withdrawal after MI attenuated or accelerated rates of post MI cardiac remodeling and MI expansion. Conclusion A blueberry-enriched diet protected the myocardium from induced ischemic damage and demonstrated the potential to attenuate the development of post MI chronic heart failure. PMID:19536295

  9. Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

    PubMed

    Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

    2014-12-01

    A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing. PMID:25632689

  10. [Nonsurgical endodontic treatment of an invaginated canine].

    PubMed

    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment. PMID:2638021